The synergistic effect of resveratrol in combination with cisplatin on apoptosis via modulating autophagy in A549 cells

Abstract

Several studies have shown that combination treatment with natural products and chemotherapy agents can improve the sensitivity and cytotoxicity of chemotherapy agents. Resveratrol, a natural product, has many biological effects including antitumor and antiviral activities, as well as vascular protective effect. The aim of this study is to investigate the synergistic anticancer effect of resveratrol in combination with cisplatin and the potential anticancer mechanisms involved in A549 cells. The results obtained from Cell Counting Kit-8 and isobolographic analysis demonstrated that combination of resveratrol and cisplatin resulted in synergistic cytotoxic effects in A549 cells. Results from Hoechst staining, flow cytometry and western blot analysis suggested that resveratrol enhanced cisplatin-mediated apoptosis. Meanwhile, the changes of LC3-II and P62 levels and formation of autophagosome suggested that resveratrol in combination with cisplatin triggered autophagy. More importantly, inhibiting autophagy by 3-methyladenine markedly attenuated the apoptosis caused by combination of resveratrol and cisplatin in A549 cells. Taken together, our study provides the first evidence that resveratrol combined with cisplatin synergistically induce apoptosis via modulating autophagic cell death in A549 cells. These findings also help us to understand the role of natural products in combination with chemotherapy agents in lung cancer.

Resveratrol Sensitizes Lung Cancer Cell to TRAIL by p53 Independent and Suppression of Akt/NF-κB Signaling

“…We then investigated the molecular mechanism underlying this apoptotic pathway. Previous reports have suggested that resveratrol has the capability to induce autophagy and might also play a role in enhancing apoptosis [54][55][56]. However, our western blot results revealed that treatment with different concentrations of resveratrol increased LC3-II accumulation and decreased p62 expression levels in A549 cells, thus confirming the activation of complete autophagy flux by lysosomal degradation (Fig.…”

Mitochondrial Dysfunction and Cytochrome C Translocation Induced by Resveratrol Are Dependent on NF-κB Activity and Facilitate TRAIL Sensitivity in Human Lung Cancers

“…Previous reports have suggested that resveratrol has the capability to induce autophagy and might also play a role in enhancing apoptosis [58][59][60]. However, our western blot results revealed that treatment with different concentrations of resveratrol increased LC3-II accumulation and decreased p62 expression levels in A549 cells, thus confirming the activation of complete autophagy flux by lysosomal degradation (Fig.…”

<p>Traditional Chinese medicine-combination therapies utilizing nanotechnology-based targeted delivery systems: a new strategy for antitumor treatment</p>

“…For instance, although cisplatin is clinically effective, it lacks selectivity for tumor tissue, resulting in serious side effects, such as kidney-function damage, 101 neurotoxicity, 102 ototoxicity, 103 and the emergence of MDR, resulting in the failure of chemotherapy. 104 In addition, longterm or high-dose cisplatin treatment can also cause severe anemia. 105 Therefore, the clinical application of single drugs, such as cisplatin, has been greatly restricted.…”