Resveratrol Enhances the Anti-Cancer Effects of Cis-Platinum on Human Cervical Cancer Cell Lines by Activating the SIRT3 Relative Anti-Oxidative Pathway

Abstract

Background: Cervical cancer exerts considerable mortality in the world. The combinations of chemotherapy with cis-platinum were the first-line treatment in late-stage cervical cancer but may cause severe adverse effects. Resveratrol (RES, 3,5,4′-trihydroxy-trans-stilbene) is a phytoalexin, and it showed anti-cancer effects but with low toxicity and side effects. Herein, we examined the anti-cancer effects of cis-platinum combined with RES in human cervical cancer cell lines.Methods: The antiproliferative effect was examined by cell counting and short-term MTT assay. Cell apoptosis was detected. The cell cycle distribution was determined by flow cytometry. Intracellular reactive oxygen species and mitochondrial transmembrane potential change were observed and calculated by confocal microscopy. The Si-RNA interference of SIRT3 in cancer cells was performed. Protein expression was checked by Western blotting.Results: RES inhibited the growth of SiHa cell lines, and it significantly enhanced the cis-platinum-induced cell apoptosis and cell cycle arresting in 48 h. The activation of the SIRT3 relative anti-oxidative pathway was proved to be the reason for the enhanced anti-cancer effects of cis-platinum and RES combination. Si-RNA interference of SIRT3 compromised the anti-cancer effect of cis-platinum and RES combination. Furthermore, the silencing of SIRT3 RNA inhibited the expression of the anti-oxidant enzyme (MnSOD, GPx, SOD-1, and CAT) and decreased the generation of H2O2 in the cis-platinum and RES combination group.Conclusion: RES enhances the anti-cancer effects of cis-platinum on SiHa cells by activating the SIRT3 relative anti-oxidative pathway. RES may act as a potential synergistic agent and be useful in the treatment of cervical cancer.

Destruction of the cellular antioxidant pool contributes to resveratrol‐induced senescence and apoptosis in lung cancer

“…In the present study, we examined cell fate decisions in the RES-treated A549 and H1299 lung cancer cell lines. Consistent with previous findings (Bian et al, 2022;Jiang et al, 2022;, RES reduced lung cancer cell viability, inhibited cell proliferation, and promoted cell senescence and apoptosis. Our results further showed that RES-induced ROS production by inhibiting Nrf2 expression in a dose-and time-dependent manner.…”

“…Many studies have confirmed that RES has antitumor potential in vitro and in vivo (Fu et al, 2021; Ko et al, 2017; Yousef et al, 2017). The anticancer effects and the underlying mechanisms of RES, such as cell proliferation inhibition (Qin et al, 2022), apoptosis induction (Jang et al, 2019), modulation of the immune system (Q. Zhang et al, 2020), and elevation effects of other anticancer drugs (Jiang et al, 2022) have been studied. However, the mechanism of action of RES remains unclear.…”

Advances in the role of resveratrol and its mechanism of action in common gynecological tumors

“… Muhanmode et al (2022) showed that RES and curcumin reversed OC-acquired CDDP resistance in vitro by significantly inhibiting the PI3K/AKT/mTOR axis. Jiang et al (2022) demonstrated that RES treatment significantly enhances the sensitivity of SiHa cells to CDDP by activating SIRT3. Specifically, combination treatment increases the levels of hydrogen peroxide (H2O2) and manganese superoxide dismutase (MnSOD) in the cells and significantly reduces mitochondrial membrane potential (ΔΨm) and ROS levels.…”

Role of Sirtuin 3 in Degenerative Diseases of the Central Nervous System

“…An NAD + -dependent deacetylase called Sirt3 participates in mitochondrial metabolic processes, including energy generation [6], the tricarboxylic acid cycle [7], and oxidative stress [8]. It has the functions of antioxidative stress [9], antiapoptosis [10], and the maintenance of metabolic homeostasis [11]. The primary source of the energy supply for the brain is the decomposition of glucose, which generates ATP.…”