Licochalcone B Induces ROS-Dependent Apoptosis in Oxaliplatin-Resistant Colorectal Cancer Cells via p38/JNK MAPK Signaling

Abstract

Licochalcone B (LCB) exhibits anticancer activity in oral cancer, lung cancer, and hepatocellular carcinoma cells. However, little is known about its antitumor mechanisms in human oxaliplatin-sensitive and -resistant colorectal cancer (CRC) cells. The purpose of the present study was to investigate the antitumor potential of LCB against human colorectal cancer in vitro and analyze its molecular mechanism of action. The viability of CRC cell lines was evaluated using the MTT assay. Flow cytometric analyses were performed to investigate the effects of LCB on apoptosis, cell cycle distribution, reactive oxygen species (ROS), mitochondrial membrane potential (MMP) dysfunction, and multi-caspase activity in CRC cells. The results demonstrated that LCB induced a reduction in cell viability, apoptosis, G2/M cell cycle arrest, ROS generation, MMP depolarization, activation of multi-caspase, and JNK/p38 MAPK. However, p38 (SB203580) and JNK (SP600125) inhibitors prevented the LCB-induced reduction in cell viability. The ROS scavenger N-acetylcysteine (NAC) inhibited LCB-induced reduction in cell viability, apoptosis, cell cycle arrest, ROS generation, MMP depolarization, and multi-caspase and JNK/p38 MAPK activities. Taken together, LCB has a potential therapeutic effect against CRC cells through the ROS-mediated JNK/p38 MAPK signaling pathway. Therefore, we expect LCB to have promising potential as an anticancer therapeutic and prophylactic agent.

GLUD1 inhibits hepatocellular carcinoma progression via ROS-mediated p38/JNK MAPK pathway activation and mitochondrial apoptosis

“…In this study, we found that GLUD1 overexpression promotes HCC cells apoptosis through ROS induced MAPKs signaling pathway activation. In recent years, studies on the activation of p38/JNK MAPK signaling pathway and the induction of tumor cell apoptosis have been confirmed and explored in liver cancer, lung cancer, pancreatic cancer, colorectal cancer, and so on [38][39][40]. MAPKs signaling pathway are taken as promising targets for cancer therapy, and some compounds that act as activators of MAPKs signaling pathway exhibit inhibitory effects on cancer progression through inducing mitochondrial apoptosis of cancer cells [41,42].…”

Phenethyl isothiocyanate inhibits the carcinogenic properties of hepatocellular carcinoma Huh7.5.1 cells by activating MAPK/PI3K-Akt/p53 signaling pathways

“…It has been demonstrated that the ERK/MAPK pathway plays a crucial role in regulating cell growth and differentiation, and its hyper-activation can trigger a cascade of intracellular responses, resulting in cell cycle arrest at the G1/S or G2/M checkpoints, thereby causing cell cycle blockage ( Kim & Choi, 2010 ). Additionally, the activation of JNK/MAPK and p38/MAPK signaling pathways may intensify the cellular response to oxidative stress, promoting the accumulation of ROS, which in turn affects the normal physiological functions of the cell ( Wang et al, 2018 ; Kwak et al, 2023 ). As a tumor suppressor protein, p53 plays a central role in how cells respond to DNA damage and stress ( Ou & Schumacher, 2018 ; Liebl & Hofmann, 2019 ; Vaddavalli & Schumacher, 2022 ).…”

Licochalcone D Inhibits Skin Epidermal Cells Transformation through the Regulation of AKT Signaling Pathways

“…Licochalcones regulate signaling pathways, including EGFR/ERK ( Gao et al ., 2021 ), PI3K/Akt/mTOR ( Xue et al ., 2018 ), p38/JNK ( Kwak et al ., 2023 ), JAK2/STAT3 ( Park et al ., 2022 ), MEK/ERK ( Park et al ., 2015 ), and MKK4/JNK ( Wu et al ., 2018 ), and their downstream protein expression. They have been shown to exert various biological effects on cancer cells, such as inducing autophagy and apoptosis and inhibiting cell proliferation, migration, and invasion ( Deng et al ., 2023 ).…”