Vitexin induces apoptosis by suppressing autophagy in multi-drug resistant colorectal cancer cells

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Title
Vitexin induces apoptosis by suppressing autophagy in multi-drug resistant colorectal cancer cells
Author(s)
M Bhardwaj; Hee Jun Cho; S Paul; R Jakhar; I Khan; Seon-Jin LeeBo Yeon Kim; M Krishnan; T P Khaket; Hee Gu Lee; S C Kang
Bibliographic Citation
Oncotarget, vol. 9, no. 3, pp. 3278-3291
Publication Year
2018
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, antiinflammatory 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-116DR), 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-116DR cells and showed cytotoxic effect in HCT-116DR 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 autophagyrelated proteins, such as ATG5, Beclin-1 and LC3-II, was markedly reduced by vitexin treatment. Furthermore, in vivo experiments showed that vitexin induced apoptosis and suppressed tumor growth in HCT-116DR xenograft model. These results revealed that vitexin induced apoptosis through suppression of autophagy in vitro and in vivo and provide insight into the therapeutic potential of vitexin for the treatment of chemo-resistant colorectal cancer
Keyword
apoptosisautophagycolorectal cancermultidrug resistancevitexin
ISSN
1949-2553
Publisher
Impact Journals
DOI
http://dx.doi.org/10.18632/oncotarget.22890
Type
Article
Appears in Collections:
Division of Biomedical Research > Immunotherapy Research Center > 1. Journal Articles
Division of Research on National Challenges > Environmental diseases research center > 1. Journal Articles
Ochang Branch Institute > Chemical Biology Research Center > 1. Journal Articles
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