Polydatin Reduces Cardiotoxicity and Enhances the Anticancer Effects of Sunitinib by Decreasing Pro-Oxidative Stress, Pro-Inflammatory Cytokines, and NLRP3 Inflammasome Expression

Figures

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  Figure 1. Cell viability (A, B), cell death determined through LDH releases (C, D), ATP content (E, F), cytochrome c release (G, H) ad apoptosis assay thorough quantification od Caspase3/7 expression (I, J) in cardiac cells (AC16 and H9C2 cell lines) after 48h of incubation with sunitinib, polydatin or both in combination. Error bars depict means ± SD. p-values for the indicated compounds relative to untreated cells are: ***p<0.001. **p<0.01. *p<0.05. ns, not significant.

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  Figure 2. Cell viability (A, B), cell death determined through LDH releases (C, D), ATP content (E, F), cytochrome c release (G, H) ad apoptosis assay thorough quantification od Caspase3/7 expression (I, J) in renal adenocarcinoma cells (769-P and A498 cell lines) after 48h of incubation with sunitinib, polydatin or both in combination. Error bars depict means ± SD. p-values for the indicated compounds relative to untreated cells are: ***p<0.001. **p<0.01. *p<0.05. ns, not significant.

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  Figure 3. Leukotrienes type B4 production by AC-16 and H9C2 cells (A) or 769-P and A498 cells (B), untreated (control) or treated with polydatin (100 and 200 µM) or sunitinib (10 µM) alone or combined to polydatin at 100 or 200 µM for 12h. Error bars depict means ± SD. p-values for the indicated compounds relative to untreated cells are: ***p<0.001. **p<0.01. *p<0.05. ns, not significant.

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  Figure 4. (A, C) Intracellular Reactive Oxygen Species (iROS) and (B, D) Malondialdeyde (MDA) quantification in cardiac cells (AC-16 and H9C2 cell lines) or human adenocarcinoma cells (769-P and A498 cell lines) untreated (control) or treated with polydatin (100 and 200 µM) or sunitinib (10 µM) alone or combined to polydatin at 100 or 200 µM for 12h. Error bars depict means ± SD. p-values for the indicated compounds relative to untreated cells are: ***p<0.001. **p<0.01. *p<0.05. ns, not significant.

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  Figure 5. (A, D) NLRP3 inflammasome (B, E) Myd88 myddosome (C, F) and p65/NF-kB (fold of control) expression in cardiac cells (AC-16 and H9C2 cell lines) and renal adenocarcinoma cells (769-P and A498 cell lines) untreated (control) or treated with polydatin (100 and 200 µM) or sunitinib (10 µM) alone or combined to polydatin at 100 or 200 µM. Error bars depict means ± SD. p-values for the indicated compounds relative to untreated cells are: ***p<0.001. **p<0.01. *p<0.05. ns, not significant.

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  Figure 6. Expression of IL-1β, IL-6, IL-8, CXCL-12, TGF-β and IL-18 in cardiac cells (A, B) (AC-16 and H9C2 cells) and renal adenocarcinoma cells (C, D) (769-P and A498 cell lines); cells were untreated (control) or treated with polydatin (100 and 200 µM) or sunitinib (10 µM) alone or combined to polydatin at 100 or 200 µM. Error bars depict means ± SD. p-values for the indicated compounds relative to untreated cells are: ***p<0.001. **p<0.01. *p<0.05. ns, not significant.

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  Figure 7. Expression of NLRP3 (A, B), IL-1β (C, D) and IL-18 (E, F) in cardiac cells (AC-16 and H9C2 cells) and renal adenocarcinoma cells (769-P and A498 cell lines); cells were untreated (control) or treated with resveratrol (100 and 200 µM) or sunitinib (10 µM) alone or combined to resveratrol at 100 or 200 µM. Error bars depict means ± SD. p-values for the indicated compounds relative to untreated cells are: ***p<0.001. **p<0.01. *p<0.05. ns, not significant.

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  Figure 8. Mechanistic illustration of chemosensitizing and cardioprotective properties of polydatin during exposure to the TKi sunitinib.