Curcumin potentiates antitumor activity of cisplatin in bladder cancer cell lines via ROS-mediated activation of ERK1/2

Abstract

Resistance of bladder cancer to cisplatin is a major obstacle to successful treatment. In the current study, we investigated the apoptotic effects of curcumin and cisplatin co-treatment in 253J-Bv(p53 wild-type) and T24(p53 mutant) bladder cancer. We found that curcumin and cisplatin co-treatment primarily targets reactive oxygen species(ROS) and extracellular regulated kinase(ERK) signaling during the apoptosis induction in bladder cancer. The apoptosis rate in 253J-Bv and T24 cells co-treated with curcumin and cisplatin was increased compared to that in cells exposed to single-agent treatment conditions. Also, caspase-3 activation and ROS production were observed in both cells treated with curcumin and cisplatin, together with upregulation of p-MEK and p-ERK1/2 signaling. NAC(ROS scavenger) and U0126(ERK inhibitor) inhibited apoptosis induced by curcumin and cisplatin. In addition, when 253J-Bv cells were co-treated with curcumin and cisplatin, p53 and p21 expression levels were markedly increased when compared to controls. Unlike 253J-Bv cells, T24 cells were co-treated with curcumin and cisplatin revealed an induction of apoptosis through decreased p-signal transducer and activator of transcription 3(STAT3) expression. Moreover, pretreatment with U0126 suppressed curcumin and cisplatin-induced upregulation of p53, p21, and p-STAT3 and downregulation of survival proteins in both cells. In conclusion, co-treatment with curcumin and cisplatin synergistically induced apoptosis through ROS-mediated activation of ERK1/2 in bladder cancer.

Artichoke Polyphenols Sensitize Human Breast Cancer Cells to Chemotherapeutic Drugs via a ROS-Mediated Downregulation of Flap Endonuclease 1

“…In light of our previous findings regarding the role of AEs as prooxidant players on breast cancer cells [27], this study has explored the ability of AEs to sensitize breast cancer cell to conventional chemotherapy through oxidative process. Based on literature data [38][39][40][41][42], our results strongly support the prooxidant role of AEs/PTX in hindering breast cancer cellular growth associated with ROS production. To further confirm the important role of ROS in enhancing the antitumor effect of the combined treatment, we demonstrate that the well-known antioxidant NAC attenuates the synergistic and antitumor effect on MDA-MB231 cells.…”

“…ROS cellular levels are thus crucial for designing advanced therapies and a future challenge in anticancer treatment [58]. There are many reports describing the prooxidant effect of polyphenols in sensitizing cancer cells to chemotherapeutic drugs through different pathways [38][39][40][41][65][66][67].…”

“…It has been shown that polyphenols can modulate multiple signaling pathways including MAPK/ERK [19,38,70,71]. By inhibiting ERK phosphorylation, curcumin helps to sensitize the cells to cisplatin by targeting FEN1 [19].…”

“…Notably, ROS-induced oxidative stress plays an important role in cancer development and progression. Among ROS-inducing agents, many phytochemicals, including curcumin [38,39], resveratrol [40,41], and epigallocatechin-3-gallate [42], have been shown to enhance the anticancer properties of chemotherapeutic agents. We have previously demonstrated a dual role of AEs, as prooxidant in breast cancer cells [25] and as antioxidant in normal hepatocyte [24] showing an inhibitory effect on growth of tumor cells with little or no toxicity on normal cells based on their differential redox status.…”

Synergistic effect of ursodeoxycholic acid on the antitumor activity of sorafenib in hepatocellular carcinoma cells via modulation of STAT3 and ERK

“…Previous studies have demonstrated that ERK activation induces apoptosis under specific conditions, such as excessive ROS generation or oxidant scavenging failure ( 25 ). According to Zuo et al ( 26 ), alternol, an antitumor agent used in the treatment of osteosarcoma, increases ROS levels by activating ERK and subsequently inhibiting STAT3 phosphorylation.…”