Vitexin Induces Apoptosis by Suppressing Autophagy in Multi-drug Resistant Colorectal Cancer Cells

Overview

Journal Oncotarget

Specialty Oncology

Date 2018 Feb 10

PMID 29423046

Citations 28

Authors

Monika Bhardwaj

Hee Jun Cho

Souren Paul

Rekha Jakhar

Imran Khan

Seon-Jin Lee

Bo-Yeon Kim

Manigandan Krishnan

Tejinder Pal Khaket

Hee Gu Lee

Sun Chul Kang

Affiliations

Soon will be listed here.

Abstract

Cancer treatment is limited due to the diverse multidrug resistance acquired by cancer cells and the collateral damage caused to adjacent normal cells by chemotherapy. The flavonoid compound vitexin exhibits anti-oxidative, anti-inflammatory and anti-tumor activity. This study elucidated the antitumor effects of vitexin and its underlying mechanisms in a multi-drug resistant human colon cancer cell line (HCT-116), which exhibits higher levels of multidrug-resistant protein 1 (MDR1) expression as compared with its parental cell line (HCT-116). Here, we observed that vitexin suppressed MDR-1 expression and activity in HCT-116 cells and showed cytotoxic effect in HCT-116 cells by inhibiting autophagy and inducing apoptosis in a concentration-dependent manner. Additionally, vitexin treatment caused cleavage of caspase-9 and caspase-3, and upregulated the expression of the pro-apoptotic proteins, BID and Bax. Moreover, the expression of autophagy-related proteins, such as ATG5, Beclin-1 and LC3-II, was markedly reduced by vitexin treatment. Furthermore, experiments showed that vitexin induced apoptosis and suppressed tumor growth in HCT-116 xenograft model. These results revealed that vitexin induced apoptosis through suppression of autophagy and and provide insight into the therapeutic potential of vitexin for the treatment of chemo-resistant colorectal cancer.

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