Resveratrol Analog 4-Bromo-Resveratrol Inhibits Gastric Cancer Stemness through the SIRT3-c-Jun N-Terminal Kinase Signaling Pathway

Yun-Shen Tai,Chun-Lin Chen,Yi-Shih Ma,Chih-Yi Chen,Hsin-Yi Tsai,Meng-Chieh Wu,Chin-Chuan Tsai,Ming-Wei Lin

doi:10.3390/cimb44010005

Abstract

Chemotherapy is the treatment of choice for gastric cancer, but the currently available therapeutic drugs have limited efficacy. Studies have suggested that gastric cancer stem cells may play a key role in drug resistance in chemotherapy. Therefore, new agents that selectively target gastric cancer stem cells in gastric tumors are urgently required. Sirtuin-3 (SIRT3) is a deacetylase that regulates mitochondrial metabolic homeostasis to maintain stemness in glioma stem cells. Targeting the mitochondrial protein SIRT3 may provide a novel therapeutic option for gastric cancer treatment. However, the mechanism by which stemness is regulated through SIRT3 inhibition in gastric cancer remains unknown. We evaluated the stemness inhibition ability of the SIRT3 inhibitor 4′-bromo-resveratrol (4-BR), an analog of resveratrol in human gastric cancer cells. Our results suggested that 4-BR inhibited gastric cancer cell stemness through the SIRT3-c-Jun N-terminal kinase pathway and may aid in gastric cancer stem-cell–targeted therapy.

Highlights

Introduction iationsGastric cancer is the most common cause of malignancy and cancer-related mortalities worldwide [1]
We evaluated the effects of 4-BR on cancer stemness and chemoresistance inhibition in gastric cancer cells
Human gastric cancer cells were seeded in 96-well dishes in quadruplicate at 6000 cells/well and cultured for 24 h before treatment

Summary

Introduction

Gastric cancer is the most common cause of malignancy and cancer-related mortalities worldwide [1]. Systemic chemotherapy with multiple drugs may be an effective strategy for patients with recurrent gastric cancer. Numerous studies have reported that chemotherapeutic resistance in gastric solid tumors results from genetic heterogeneity in tumor cells. Studies have suggested that cancer stem cells (CSCs) contribute to chemotherapy drug resistance [2]. CSCs are a subpopulation of tumor masses with the ability to self-renew, maintain stemness, and cause cancer recurrence [3]. CSCs may be a novel target for anticancer strategies and gastric cancer therapy in precision medicine [2]

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