Vitexin induces apoptosis by suppressing autophagy in multidrug resistant colorectal cancer cells

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

Research output: Contribution to journalArticlepeer-review

36 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)3278-3291
Number of pages14
JournalOncotarget
Volume9
Issue number3
DOIs
StatePublished - 2018
Externally publishedYes

Bibliographical note

Funding Information:
This research was funded by the National Research Foundation (NRF) of South Korea (2016R1A2B4009227, 2017R1A2B2005629, 2016H1D3A1938249 and 2017R1D1A1B03036569).

Publisher Copyright:
© Bhardwaj et al.

Keywords

  • Apoptosis
  • Autophagy
  • Colorectal cancer
  • Multidrug resistance
  • Vitexin

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