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PMC12141184
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Curcumin inhibits IFN-γ induced PD-L1 expression via reduction of STAT1 Phosphorylation in A549 non-small cell lung cancer cells.
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This trend correlated with sustained STAT1 phosphorylation, indicating that IFN-γ-driven STAT1 activation plays a key role in PD-L1 upregulation in A549 cells (Fig. 1).
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PMC12141184
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Curcumin inhibits IFN-γ induced PD-L1 expression via reduction of STAT1 Phosphorylation in A549 non-small cell lung cancer cells.
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To further assess the effect of IFN-γ on PD-L1 regulation, we performed quantitative real-time PCR (qRT-PCR) to measure PD-L1 mRNA expression levels in A549 cells treated with IFN-γ (500 U/ml) for different time points.
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PMC12141184
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Curcumin inhibits IFN-γ induced PD-L1 expression via reduction of STAT1 Phosphorylation in A549 non-small cell lung cancer cells.
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The results demonstrated a time-dependent increase in PD-L1 mRNA expression.
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PMC12141184
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Curcumin inhibits IFN-γ induced PD-L1 expression via reduction of STAT1 Phosphorylation in A549 non-small cell lung cancer cells.
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At 6 h, PD-L1 mRNA levels were significantly upregulated by approximately 1.8-fold compared to untreated control cells (p < 0.05).
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PMC12141184
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Curcumin inhibits IFN-γ induced PD-L1 expression via reduction of STAT1 Phosphorylation in A549 non-small cell lung cancer cells.
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By 12 h, PD-L1 expression increased further to 2.9-fold (p < 0.01), and by 24 h, the induction reached a peak with a 3.8-fold increase (p < 0.001).
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PMC12141184
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Curcumin inhibits IFN-γ induced PD-L1 expression via reduction of STAT1 Phosphorylation in A549 non-small cell lung cancer cells.
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These findings confirm that IFN-γ robustly upregulates PD-L1 expression at the transcriptional level over time, supporting its role in immune evasion mechanisms (Fig. 3).Fig.
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PMC12141184
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Curcumin inhibits IFN-γ induced PD-L1 expression via reduction of STAT1 Phosphorylation in A549 non-small cell lung cancer cells.
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3qRT-PCR analysis showing time-dependent upregulation of PD-L1 mRNA expression in A549 cells following IFN-γ treatment.
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PMC12141184
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Curcumin inhibits IFN-γ induced PD-L1 expression via reduction of STAT1 Phosphorylation in A549 non-small cell lung cancer cells.
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A549 cells were treated with 500 U/mL of IFN-γ for 6, 12, and 24 h. Total RNA was extracted and analyzed by qRT-PCR to measure PD-L1 mRNA expression levels.
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PMC12141184
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Curcumin inhibits IFN-γ induced PD-L1 expression via reduction of STAT1 Phosphorylation in A549 non-small cell lung cancer cells.
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Data are presented as mean ± SD relative to untreated controls.
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PMC12141184
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Curcumin inhibits IFN-γ induced PD-L1 expression via reduction of STAT1 Phosphorylation in A549 non-small cell lung cancer cells.
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Statistical significance is indicated (*p < 0.05, **p < 0.01, ***p < 0.001) qRT-PCR analysis showing time-dependent upregulation of PD-L1 mRNA expression in A549 cells following IFN-γ treatment.
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PMC12141184
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Curcumin inhibits IFN-γ induced PD-L1 expression via reduction of STAT1 Phosphorylation in A549 non-small cell lung cancer cells.
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A549 cells were treated with 500 U/mL of IFN-γ for 6, 12, and 24 h. Total RNA was extracted and analyzed by qRT-PCR to measure PD-L1 mRNA expression levels.
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PMC12141184
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Curcumin inhibits IFN-γ induced PD-L1 expression via reduction of STAT1 Phosphorylation in A549 non-small cell lung cancer cells.
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Data are presented as mean ± SD relative to untreated controls.
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PMC12141184
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Curcumin inhibits IFN-γ induced PD-L1 expression via reduction of STAT1 Phosphorylation in A549 non-small cell lung cancer cells.
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Statistical significance is indicated (*p < 0.05, **p < 0.01, ***p < 0.001) To investigate whether curcumin inhibits IFN-γ-induced STAT1 phosphorylation, A549 cells were pretreated with curcumin (50 µM) for 2 h before stimulation with IFN-γ (500 U/ml) for 24 h. Western blot analysis revealed a significant reduction in phosphorylated STAT1 (p-STAT1, Tyr701) levels in curcumin-pretreated cells, with a 68% decrease compared to IFN-γ-treated cells alone (p < 0.001).
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PMC12141184
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Curcumin inhibits IFN-γ induced PD-L1 expression via reduction of STAT1 Phosphorylation in A549 non-small cell lung cancer cells.
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Notably, total STAT1 protein levels remained unchanged, confirming that the decrease in p-STAT1 was due to inhibition of phosphorylation rather than reduced STAT1 expression.
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PMC12141184
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Curcumin inhibits IFN-γ induced PD-L1 expression via reduction of STAT1 Phosphorylation in A549 non-small cell lung cancer cells.
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Additionally, PD-L1 expression, which is regulated by STAT1 activation, was also markedly reduced in curcumin-treated cells, with 50 µM curcumin reducing PD-L1 levels by 72% compared to IFN-γ-treated cells (p < 0.01).
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PMC12141184
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Curcumin inhibits IFN-γ induced PD-L1 expression via reduction of STAT1 Phosphorylation in A549 non-small cell lung cancer cells.
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These findings indicate that curcumin effectively suppresses IFN-γ-induced STAT1 activation and its downstream signaling, including PD-L1 upregulation, in A549 cells (Fig. 4).Fig.
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PMC12141184
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Curcumin inhibits IFN-γ induced PD-L1 expression via reduction of STAT1 Phosphorylation in A549 non-small cell lung cancer cells.
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4Western blot analysis showing the effect of curcumin on IFN-γ-induced STAT1 phosphorylation and PD-L1 expression in A549 cells.
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PMC12141184
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Curcumin inhibits IFN-γ induced PD-L1 expression via reduction of STAT1 Phosphorylation in A549 non-small cell lung cancer cells.
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A549 cells were pretreated with curcumin (50 µM) for 2 h, followed by stimulation with IFN-γ (500 U/mL).
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PMC12141184
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Curcumin inhibits IFN-γ induced PD-L1 expression via reduction of STAT1 Phosphorylation in A549 non-small cell lung cancer cells.
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Protein lysates were collected and analyzed by Western blot for phosphorylated STAT1 (Tyr701), total STAT1, and PD-L1 expression.
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PMC12141184
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Curcumin inhibits IFN-γ induced PD-L1 expression via reduction of STAT1 Phosphorylation in A549 non-small cell lung cancer cells.
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β-Actin was used as a loading control Western blot analysis showing the effect of curcumin on IFN-γ-induced STAT1 phosphorylation and PD-L1 expression in A549 cells.
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PMC12141184
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Curcumin inhibits IFN-γ induced PD-L1 expression via reduction of STAT1 Phosphorylation in A549 non-small cell lung cancer cells.
|
A549 cells were pretreated with curcumin (50 µM) for 2 h, followed by stimulation with IFN-γ (500 U/mL).
|
PMC12141184
|
Curcumin inhibits IFN-γ induced PD-L1 expression via reduction of STAT1 Phosphorylation in A549 non-small cell lung cancer cells.
|
Protein lysates were collected and analyzed by Western blot for phosphorylated STAT1 (Tyr701), total STAT1, and PD-L1 expression.
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PMC12141184
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Curcumin inhibits IFN-γ induced PD-L1 expression via reduction of STAT1 Phosphorylation in A549 non-small cell lung cancer cells.
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β-Actin was used as a loading control Since STAT1 regulates the expression of multiple ISGs involved in immune evasion, we next evaluated the effect of curcumin on the expression of ISG15 and SOCS1.
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PMC12141184
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Curcumin inhibits IFN-γ induced PD-L1 expression via reduction of STAT1 Phosphorylation in A549 non-small cell lung cancer cells.
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qRT-PCR analysis showed that IFN-γ significantly upregulated ISG15 and SOCS1 mRNA expression by 3.2-fold and 4.5-fold, respectively, compared to untreated controls (p < 0.001).
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PMC12141184
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Curcumin inhibits IFN-γ induced PD-L1 expression via reduction of STAT1 Phosphorylation in A549 non-small cell lung cancer cells.
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However, pretreatment with curcumin (50 µM) led to a suppression of ISG15 (54% reduction) and SOCS1 (63% reduction) expression, further supporting the role of curcumin in inhibiting IFN-γ-driven STAT1 signaling (Fig. 5).Fig.
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PMC12141184
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Curcumin inhibits IFN-γ induced PD-L1 expression via reduction of STAT1 Phosphorylation in A549 non-small cell lung cancer cells.
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5qRT-PCR analysis showing the effect of curcumin on IFN-γ-induced expression of interferon-stimulated genes (ISGs) in A549 cells.
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PMC12141184
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Curcumin inhibits IFN-γ induced PD-L1 expression via reduction of STAT1 Phosphorylation in A549 non-small cell lung cancer cells.
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A549 cells were treated with IFN-γ (500 U/mL) for 24 h, with or without curcumin pretreatment (50 µM for 2 h).
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PMC12141184
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Curcumin inhibits IFN-γ induced PD-L1 expression via reduction of STAT1 Phosphorylation in A549 non-small cell lung cancer cells.
|
Total RNA was extracted and analyzed by qRT-PCR for SOCS1 and ISG15 mRNA expression.
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PMC12141184
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Curcumin inhibits IFN-γ induced PD-L1 expression via reduction of STAT1 Phosphorylation in A549 non-small cell lung cancer cells.
|
Data are presented as mean ± SD.
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PMC12141184
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Curcumin inhibits IFN-γ induced PD-L1 expression via reduction of STAT1 Phosphorylation in A549 non-small cell lung cancer cells.
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Statistical significance is indicated (*p < 0.05, **p < 0.01, ***p < 0.001) qRT-PCR analysis showing the effect of curcumin on IFN-γ-induced expression of interferon-stimulated genes (ISGs) in A549 cells.
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PMC12141184
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Curcumin inhibits IFN-γ induced PD-L1 expression via reduction of STAT1 Phosphorylation in A549 non-small cell lung cancer cells.
|
A549 cells were treated with IFN-γ (500 U/mL) for 24 h, with or without curcumin pretreatment (50 µM for 2 h).
|
PMC12141184
|
Curcumin inhibits IFN-γ induced PD-L1 expression via reduction of STAT1 Phosphorylation in A549 non-small cell lung cancer cells.
|
Total RNA was extracted and analyzed by qRT-PCR for SOCS1 and ISG15 mRNA expression.
|
PMC12141184
|
Curcumin inhibits IFN-γ induced PD-L1 expression via reduction of STAT1 Phosphorylation in A549 non-small cell lung cancer cells.
|
Data are presented as mean ± SD.
|
PMC12141184
|
Curcumin inhibits IFN-γ induced PD-L1 expression via reduction of STAT1 Phosphorylation in A549 non-small cell lung cancer cells.
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Statistical significance is indicated (*p < 0.05, **p < 0.01, ***p < 0.001) To evaluate the time-dependent effects of curcumin on IFN-γ-induced growth suppression, cell viability was assessed using the Resazurin assay at 0, 12, 24, and 48 h following treatment.
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PMC12141184
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Curcumin inhibits IFN-γ induced PD-L1 expression via reduction of STAT1 Phosphorylation in A549 non-small cell lung cancer cells.
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At 12 h, a modest reduction in cell viability (10%) was observed in response to IFN-γ and curcumin co-treatment.
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PMC12141184
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Curcumin inhibits IFN-γ induced PD-L1 expression via reduction of STAT1 Phosphorylation in A549 non-small cell lung cancer cells.
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By 24 h, cell viability had decreased further (21% reduction), consistent with previous findings on IFN-γ-mediated cytotoxicity in A549 cells.
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PMC12141184
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Curcumin inhibits IFN-γ induced PD-L1 expression via reduction of STAT1 Phosphorylation in A549 non-small cell lung cancer cells.
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Notably, at 48 h, the combination of curcumin and IFN-γ resulted in a 47% reduction in cell viability, demonstrating a significant time-dependent enhancement of IFN-γ’s anti-proliferative effects (p < 0.01).
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PMC12141184
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Curcumin inhibits IFN-γ induced PD-L1 expression via reduction of STAT1 Phosphorylation in A549 non-small cell lung cancer cells.
|
These findings suggest that curcumin sensitizes NSCLC cells to IFN-γ-induced growth suppression in a time-dependent manner, highlighting its potential as a therapeutic adjuvant (Fig. 6).Fig.
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PMC12141184
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Curcumin inhibits IFN-γ induced PD-L1 expression via reduction of STAT1 Phosphorylation in A549 non-small cell lung cancer cells.
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6Resazurin assay showing the effect of curcumin and IFN-γ co-treatment on cell viability in A549 NSCLC cells.
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PMC12141184
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Curcumin inhibits IFN-γ induced PD-L1 expression via reduction of STAT1 Phosphorylation in A549 non-small cell lung cancer cells.
|
A549 cells were treated with curcumin (50 µM) and IFN-γ (500 U/mL) for 12, 24, and 48 h. Cell viability was assessed using the Resazurin assay.
|
PMC12141184
|
Curcumin inhibits IFN-γ induced PD-L1 expression via reduction of STAT1 Phosphorylation in A549 non-small cell lung cancer cells.
|
Data are presented as mean ± SD, showing a time-dependent decrease in viability with combination treatment.
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PMC12141184
|
Curcumin inhibits IFN-γ induced PD-L1 expression via reduction of STAT1 Phosphorylation in A549 non-small cell lung cancer cells.
|
Statistical significance is indicated (*p < 0.05, **p < 0.01, ***p < 0.001) Resazurin assay showing the effect of curcumin and IFN-γ co-treatment on cell viability in A549 NSCLC cells.
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PMC12141184
|
Curcumin inhibits IFN-γ induced PD-L1 expression via reduction of STAT1 Phosphorylation in A549 non-small cell lung cancer cells.
|
A549 cells were treated with curcumin (50 µM) and IFN-γ (500 U/mL) for 12, 24, and 48 h. Cell viability was assessed using the Resazurin assay.
|
PMC12141184
|
Curcumin inhibits IFN-γ induced PD-L1 expression via reduction of STAT1 Phosphorylation in A549 non-small cell lung cancer cells.
|
Data are presented as mean ± SD, showing a time-dependent decrease in viability with combination treatment.
|
PMC12141184
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Curcumin inhibits IFN-γ induced PD-L1 expression via reduction of STAT1 Phosphorylation in A549 non-small cell lung cancer cells.
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Statistical significance is indicated (*p < 0.05, **p < 0.01, ***p < 0.001) Immune evasion remains a significant challenge in the treatment of NSCLC, with PD-L1 upregulation being one of the primary mechanisms by which tumors escape immune surveillance (Cui et al. 2024).
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PMC12141184
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Curcumin inhibits IFN-γ induced PD-L1 expression via reduction of STAT1 Phosphorylation in A549 non-small cell lung cancer cells.
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The IFN-γ/STAT1 signaling pathway plays a crucial role in PD-L1 regulation, enabling tumor cells to suppress T-cell-mediated immune responses and resist immune checkpoint blockade therapy (Padmanabhan et al. 2022).
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PMC12141184
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Curcumin inhibits IFN-γ induced PD-L1 expression via reduction of STAT1 Phosphorylation in A549 non-small cell lung cancer cells.
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In this study, we investigated how IFN-γ-induced STAT1 phosphorylation leads to PD-L1 upregulation in A549 cells and explored the potential of curcumin, a bioactive polyphenol with known anti-inflammatory and anti-cancer properties, as a therapeutic agent capable of modulating this pathway.
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PMC12141184
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Curcumin inhibits IFN-γ induced PD-L1 expression via reduction of STAT1 Phosphorylation in A549 non-small cell lung cancer cells.
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Our findings provide strong evidence that curcumin inhibits IFN-γ-induced STAT1 activation, thereby reducing PD-L1 expression and enhancing the anti-proliferative effects of IFN-γ in NSCLC.
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PMC12141184
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Curcumin inhibits IFN-γ induced PD-L1 expression via reduction of STAT1 Phosphorylation in A549 non-small cell lung cancer cells.
|
Consistent with previous studies, we observed that IFN-γ induces a robust phosphorylation of STAT1 at Tyr701 in A549 cells, leading to its nuclear translocation and subsequent activation of target genes, including PD-L1.
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PMC12141184
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Curcumin inhibits IFN-γ induced PD-L1 expression via reduction of STAT1 Phosphorylation in A549 non-small cell lung cancer cells.
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The kinetics of STAT1 phosphorylation followed a time-dependent pattern, with phosphorylation detected as early as 2 h, peaking at 6 h, and remaining elevated up to 24 h. These results are in agreement with earlier reports that demonstrated a similar pattern of IFN-γ-induced STAT1 activation in various cancer models, including melanoma (Schmitt et al. 2012), colorectal cancer (Zhao et al. 2020), and lung adenocarcinoma (Gao et al. 2018).
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PMC12141184
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Curcumin inhibits IFN-γ induced PD-L1 expression via reduction of STAT1 Phosphorylation in A549 non-small cell lung cancer cells.
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STAT1 phosphorylation is a prerequisite for its dimerization and nuclear translocation, which is required for the transcriptional activation of ISGs (Wang et al. 2017).
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PMC12141184
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Curcumin inhibits IFN-γ induced PD-L1 expression via reduction of STAT1 Phosphorylation in A549 non-small cell lung cancer cells.
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Immunofluorescence analysis confirmed that IFN-γ treatment led to a marked accumulation of p-STAT1 in the nucleus, reinforcing the notion that STAT1 plays a crucial role in IFN-γ-mediated transcriptional regulation.
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PMC12141184
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Curcumin inhibits IFN-γ induced PD-L1 expression via reduction of STAT1 Phosphorylation in A549 non-small cell lung cancer cells.
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These findings align with studies showing that sustained STAT1 activation promotes an immunosuppressive tumor microenvironment by inducing PD-L1 expression and other immune-regulatory genes.
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PMC12141184
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Curcumin inhibits IFN-γ induced PD-L1 expression via reduction of STAT1 Phosphorylation in A549 non-small cell lung cancer cells.
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The upregulation of PD-L1 in response to IFN-γ was confirmed at both the mRNA and protein levels, as demonstrated by qRT-PCR and Western blotting.
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PMC12141184
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Curcumin inhibits IFN-γ induced PD-L1 expression via reduction of STAT1 Phosphorylation in A549 non-small cell lung cancer cells.
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The increased surface expression of PD-L1 following IFN-γ treatment highlights the functional significance of this regulation, as surface PD-L1 interacts with PD- 1 on T cells to inhibit anti-tumor immune responses (Arak et al. 2021).
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PMC12141184
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Curcumin inhibits IFN-γ induced PD-L1 expression via reduction of STAT1 Phosphorylation in A549 non-small cell lung cancer cells.
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These results are in accordance with previous reports showing that IFN-γ is one of the most potent inducers of PD-L1 in NSCLC, facilitating immune escape and tumor progression (Pawelczyk et al. 2019).
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PMC12141184
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Curcumin inhibits IFN-γ induced PD-L1 expression via reduction of STAT1 Phosphorylation in A549 non-small cell lung cancer cells.
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Additionally, the use of fludarabine, a STAT1 inhibitor, significantly attenuated IFN-γ-induced PD-L1 expression, confirming that STAT1 is the primary mediator of this regulatory axis.
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PMC12141184
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Curcumin inhibits IFN-γ induced PD-L1 expression via reduction of STAT1 Phosphorylation in A549 non-small cell lung cancer cells.
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This finding corroborates prior studies demonstrating that STAT1-deficient cells fail to upregulate PD-L1 in response to IFN-γ, emphasizing the centrality of STAT1 in this pathway.
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PMC12141184
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Curcumin inhibits IFN-γ induced PD-L1 expression via reduction of STAT1 Phosphorylation in A549 non-small cell lung cancer cells.
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One of the most significant findings of this study is the ability of curcumin to inhibit IFN-γ-induced STAT1 activation and PD-L1 expression in A549 cells.
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PMC12141184
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Curcumin inhibits IFN-γ induced PD-L1 expression via reduction of STAT1 Phosphorylation in A549 non-small cell lung cancer cells.
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Western blot analysis revealed that curcumin suppressed STAT1 phosphorylation in a dose-dependent manner, with the highest concentration (50 µM) reducing phosphorylation by 68%.
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PMC12141184
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Curcumin inhibits IFN-γ induced PD-L1 expression via reduction of STAT1 Phosphorylation in A549 non-small cell lung cancer cells.
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This effect was not due to a decrease in total STAT1 protein levels, indicating that curcumin selectively inhibits STAT1 activation rather than its expression.
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PMC12141184
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Curcumin inhibits IFN-γ induced PD-L1 expression via reduction of STAT1 Phosphorylation in A549 non-small cell lung cancer cells.
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Previous studies have reported that curcumin can interfere with JAK-STAT signaling in other cancer types.
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PMC12141184
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Curcumin inhibits IFN-γ induced PD-L1 expression via reduction of STAT1 Phosphorylation in A549 non-small cell lung cancer cells.
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Curcumin directly inhibits the phosphorylation of STAT3, a key component of the JAK-STAT signaling pathway in breast cancer (Golmohammadi et al. 2024) and prostate cancer (Li et al. 2024), as well as the downregulation of the STAT1 in melanoma (Xu et al. 2018), but its specific effect on STAT1 in IFN-γ-stimulated NSCLC cells had not been previously explored.
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PMC12141184
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Curcumin inhibits IFN-γ induced PD-L1 expression via reduction of STAT1 Phosphorylation in A549 non-small cell lung cancer cells.
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Our findings extend these observations by demonstrating that curcumin effectively blocks STAT1 activation in lung cancer cells, preventing the downstream induction of PD-L1.
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PMC12141184
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Curcumin inhibits IFN-γ induced PD-L1 expression via reduction of STAT1 Phosphorylation in A549 non-small cell lung cancer cells.
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The suppression of PD-L1 expression by curcumin was observed at both the transcriptional and translational levels, as evidenced by qRT-PCR and Western blotting.
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PMC12141184
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Curcumin inhibits IFN-γ induced PD-L1 expression via reduction of STAT1 Phosphorylation in A549 non-small cell lung cancer cells.
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This finding is particularly relevant in the context of NSCLC, where high PD-L1 expression correlates with poor prognosis and resistance to immunotherapy.
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PMC12141184
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Curcumin inhibits IFN-γ induced PD-L1 expression via reduction of STAT1 Phosphorylation in A549 non-small cell lung cancer cells.
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Previous studies have reported that curcumin downregulates PD-L1 in other cancer models, such as melanoma (Xu et al. 2018) and hepatocellular carcinoma (Guo et al. 2021), but the specific inhibition of IFN-γ-induced PD-L1 expression in NSCLC had not been thoroughly investigated.
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PMC12141184
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Curcumin inhibits IFN-γ induced PD-L1 expression via reduction of STAT1 Phosphorylation in A549 non-small cell lung cancer cells.
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Our study provides the first evidence that curcumin can effectively suppress IFN-γ-mediated PD-L1 upregulation in lung cancer cells via STAT1 pathway, highlighting its potential as an immune-modulatory agent.
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PMC12141184
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Curcumin inhibits IFN-γ induced PD-L1 expression via reduction of STAT1 Phosphorylation in A549 non-small cell lung cancer cells.
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In addition to PD-L1, STAT1 regulates the expression of multiple ISGs involved in immune evasion, including SOCS1 (Ilangumaran et al. 2024) and ISG15 (Desai 2015).
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PMC12141184
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Curcumin inhibits IFN-γ induced PD-L1 expression via reduction of STAT1 Phosphorylation in A549 non-small cell lung cancer cells.
|
Our results demonstrated that IFN-γ significantly upregulated both SOCS1 and ISG15, reinforcing the notion that IFN-γ signaling contributes to an immunosuppressive tumor microenvironment.
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PMC12141184
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Curcumin inhibits IFN-γ induced PD-L1 expression via reduction of STAT1 Phosphorylation in A549 non-small cell lung cancer cells.
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Curcumin pretreatment, however, led to a significant reduction in both SOCS1 and ISG15 expression, further supporting its ability to interfere with IFN-γ-driven STAT1 signaling.
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PMC12141184
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Curcumin inhibits IFN-γ induced PD-L1 expression via reduction of STAT1 Phosphorylation in A549 non-small cell lung cancer cells.
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SOCS1 is known to act as a feedback inhibitor of JAK-STAT signaling (Liau et al. 2018), but paradoxically, its overexpression in tumors has been associated with immune escape mechanisms.
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PMC12141184
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Curcumin inhibits IFN-γ induced PD-L1 expression via reduction of STAT1 Phosphorylation in A549 non-small cell lung cancer cells.
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By suppressing SOCS1 expression, curcumin may enhance the responsiveness of tumor cells to immune-mediated clearance.
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PMC12141184
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Curcumin inhibits IFN-γ induced PD-L1 expression via reduction of STAT1 Phosphorylation in A549 non-small cell lung cancer cells.
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Similarly, ISG15 has been implicated in tumor progression and resistance to therapy (Meng et al. 2024), suggesting that its downregulation by curcumin may have additional therapeutic benefits.
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PMC12141184
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Curcumin inhibits IFN-γ induced PD-L1 expression via reduction of STAT1 Phosphorylation in A549 non-small cell lung cancer cells.
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Finally, we observed that curcumin enhances the anti-proliferative effect of IFN-γ in A549 cells.
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PMC12141184
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Curcumin inhibits IFN-γ induced PD-L1 expression via reduction of STAT1 Phosphorylation in A549 non-small cell lung cancer cells.
|
While IFN-γ alone resulted in a modest reduction in cell viability (21%), the combination of IFN-γ and curcumin led to a significantly greater reduction (47%), suggesting a synergistic effect.
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PMC12141184
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Curcumin inhibits IFN-γ induced PD-L1 expression via reduction of STAT1 Phosphorylation in A549 non-small cell lung cancer cells.
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These findings align with previous reports that curcumin enhances the anti-tumor activity of cytokines by modulating cell cycle regulators and apoptotic pathways (Hu et al. 2018).
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PMC12141184
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Curcumin inhibits IFN-γ induced PD-L1 expression via reduction of STAT1 Phosphorylation in A549 non-small cell lung cancer cells.
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The precise mechanism by which curcumin sensitizes NSCLC cells to IFN-γ-induced growth suppression remains to be elucidated, but it may involve inhibition of survival pathways downstream of STAT1 activation.
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PMC12141184
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Curcumin inhibits IFN-γ induced PD-L1 expression via reduction of STAT1 Phosphorylation in A549 non-small cell lung cancer cells.
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Given that STAT1 has been implicated in both pro-apoptotic and pro-survival signaling, the net effect of its inhibition may depend on the cellular context and additional regulatory factors.
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PMC12141184
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Curcumin inhibits IFN-γ induced PD-L1 expression via reduction of STAT1 Phosphorylation in A549 non-small cell lung cancer cells.
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In conclusion, our study provides novel evidence that IFN-γ induces PD-L1 expression in NSCLC cells via STAT1 activation and that curcumin effectively inhibits this process by suppressing STAT1 phosphorylation and nuclear translocation.
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PMC12141184
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Curcumin inhibits IFN-γ induced PD-L1 expression via reduction of STAT1 Phosphorylation in A549 non-small cell lung cancer cells.
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Furthermore, curcumin downregulates IFN-γ-induced ISGs and enhances IFN-γ-mediated tumor cell growth suppression, highlighting its potential as a therapeutic adjuvant in NSCLC.
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PMC12141184
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Curcumin inhibits IFN-γ induced PD-L1 expression via reduction of STAT1 Phosphorylation in A549 non-small cell lung cancer cells.
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These findings suggest that curcumin could be used to improve the efficacy of immune checkpoint inhibitors by reducing tumor immune evasion.
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PMC12141184
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Curcumin inhibits IFN-γ induced PD-L1 expression via reduction of STAT1 Phosphorylation in A549 non-small cell lung cancer cells.
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Future studies should focus on elucidating the precise molecular mechanisms underlying curcumin’s effects on STAT1 signaling and investigating its potential synergistic effects with existing immunotherapies in preclinical and clinical settings.
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PMC5785775
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Generating Focused Molecule Libraries for Drug Discovery with Recurrent Neural Networks.
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In de novo drug design, computational strategies are used to generate novel molecules with good affinity to the desired biological target.
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PMC5785775
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Generating Focused Molecule Libraries for Drug Discovery with Recurrent Neural Networks.
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In this work, we show that recurrent neural networks can be trained as generative models for molecular structures, similar to statistical language models in natural language processing.
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PMC5785775
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Generating Focused Molecule Libraries for Drug Discovery with Recurrent Neural Networks.
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We demonstrate that the properties of the generated molecules correlate very well with the properties of the molecules used to train the model.
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PMC5785775
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Generating Focused Molecule Libraries for Drug Discovery with Recurrent Neural Networks.
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In order to enrich libraries with molecules active toward a given biological target, we propose to fine-tune the model with small sets of molecules, which are known to be active against that target.
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PMC5785775
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Generating Focused Molecule Libraries for Drug Discovery with Recurrent Neural Networks.
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Against Staphylococcus aureus, the model reproduced 14% of 6051 hold-out test molecules that medicinal chemists designed, whereas against Plasmodium falciparum (Malaria), it reproduced 28% of 1240 test molecules.
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PMC5785775
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Generating Focused Molecule Libraries for Drug Discovery with Recurrent Neural Networks.
|
When coupled with a scoring function, our model can perform the complete de novo drug design cycle to generate large sets of novel molecules for drug discovery.
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PMC5785775
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Generating Focused Molecule Libraries for Drug Discovery with Recurrent Neural Networks.
|
Chemistry is the language of nature.
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PMC5785775
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Generating Focused Molecule Libraries for Drug Discovery with Recurrent Neural Networks.
|
Chemists speak it fluently and have made their discipline one of the true contributors to human well-being, which has “change[d] the way you live and die”.
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PMC5785775
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Generating Focused Molecule Libraries for Drug Discovery with Recurrent Neural Networks.
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This is particularly true for medicinal chemistry.
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PMC5785775
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Generating Focused Molecule Libraries for Drug Discovery with Recurrent Neural Networks.
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However, creating novel drugs is an extraordinarily hard and complex problem.
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PMC5785775
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Generating Focused Molecule Libraries for Drug Discovery with Recurrent Neural Networks.
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One of the many challenges in drug design is the sheer size of the search space for novel molecules.
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PMC5785775
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Generating Focused Molecule Libraries for Drug Discovery with Recurrent Neural Networks.
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It has been estimated that 10 drug-like molecules could possibly be synthetically accessible.
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PMC5785775
|
Generating Focused Molecule Libraries for Drug Discovery with Recurrent Neural Networks.
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Chemists have to select and examine molecules from this large space to find molecules that are active toward a biological target.
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PMC5785775
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Generating Focused Molecule Libraries for Drug Discovery with Recurrent Neural Networks.
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Active means for example that a molecule binds to a biomolecule, which causes an effect in the living organism, or inhibits replication of bacteria.
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PMC5785775
|
Generating Focused Molecule Libraries for Drug Discovery with Recurrent Neural Networks.
|
Modern high-throughput screening techniques allow testing of molecules on the order of 10 in the lab.
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PMC5785775
|
Generating Focused Molecule Libraries for Drug Discovery with Recurrent Neural Networks.
|
However, larger experiments will get prohibitively expensive.
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PMC5785775
|
Generating Focused Molecule Libraries for Drug Discovery with Recurrent Neural Networks.
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Given this practical limitation of in vitro experiments, it is desirable to have computational tools to narrow down the enormous search space.
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