Resveratrol promotes sensitization to Doxorubicin by inhibiting epithelial‐mesenchymal transition and modulating SIRT1/β‐catenin signaling pathway in breast cancer

Abstract

Breast cancer is one of the leading fatal diseases for women worldwide who cannot have surgery typically have to rely on systemic chemotherapy to extend their survival. Doxorubicin (DOX) is one of the most commonly used chemotherapeutic agents against breast cancer, but acquired resistance to DOX can seriously impede the efficacy of chemotherapy, leading to poor prognosis and recurrences of cancer. Resveratrol (RES) is a phytoalexin with pharmacological antitumor properties, but its underlying mechanisms are not clearly understood in the treatment of DOX‐resistant breast cancer. We used cell viability assays, cell scratch tests, and transwell assays combined with Western blotting and immunofluorescent staining to evaluate the effects of RES on chemoresistance and the epithelial‐mesenchymal transitions (EMTs) in adriamycin‐resistant MCF7/ADR breast cancer cells, and to investigate its underlying mechanisms. The results showed that a treatment of RES combining with DOX effectively inhibited cell growth, suppressed cell migration, and promoted cell apoptosis. RES reversed EMT properties of MCF7/ADR cells by modulating the connection between SIRT1 and β‐catenin, which provides a hopeful therapeutic avenue to conquer DOX‐resistance and thereby prolong survival rates in breast cancer patients.

The E-Cadherin and N-Cadherin Switch in Epithelial-to-Mesenchymal Transition: Signaling, Therapeutic Implications, and Challenges

“…Adriamycin was shown to induce E-cadherin-mediated cell–cell adhesion by increasing the expression of E-cadherin and β-catenin while decreasing the expression of Mucin 1 in YMB-S breast cancer cells [209]. In adriamycin-resistant MCF7/ADR breast cancer cells resveratrol sensitized the cells to doxorubicin and promoted cell apoptosis [210]. Resveratrol reversed EMT in MCF7/ADR cells by inhibiting the connection between SIRT1 and β-catenin [210].…”

Resveratrol, curcumin, paclitaxel and miRNAs mediated regulation of PI3K/Akt/mTOR pathway: go four better to treat bladder cancer

“…Resveratrol therapeutic potential also includes its ability to treat BC resistant to numerous drugs either by re-sensitizing cancer cells to certain drug or by inhibiting cell growth by adopting alternative apoptosis route [ 94 – 97 ]. It re-sensitized cancer cells to doxorubicin in a dose-dependent manner [ 96 , 98 , 99 ]. It has a pro-apoptotic effect on taxol resistant BC cell lines by inhibiting cell growth beyond S-phase [ 100 ].…”

Quercetin Enhances the Anti-Tumor Effects of BET Inhibitors by Suppressing hnRNPA1

“…They can also enhance the efficacy of different cancer drugs. For example, Curcumin and Resveratrol have been reported to sensitize cancer cells to conventional chemotherapy drugs such as cisplatin [2,3,4], paclitaxel [5,6], and doxorubicin [7,8,9,10]. There is also increasing interest in evaluating the ability of these natural compounds to enhance the efficacy of novel cancer therapeutics.…”