Portal de Periódicos da CAPES

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

2017; Impact Journals LLC; Volume: 9; Issue: 3 Linguagem: Inglês

10.18632/oncotarget.22890

1949-2553

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,

Ginger and Zingiberaceae research

// Monika Bhardwaj 1, * , Hee Jun Cho 2, * , Souren Paul 1 , Rekha Jakhar 1 , Imran Khan 1 , Seon-Jin Lee 2, 3 , Bo-Yeon Kim 3, 4 , Manigandan Krishnan 1 , Tejinder Pal Khaket 1 , Hee Gu Lee 2, 3 and Sun Chul Kang 1 1 Department of Biotechnology, Daegu University, Kyoungsan, Kyoungbook, Republic of Korea 2 Immunotherapy Convergence Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, Republic of Korea 3 Department of Biomolecular Science, University of Science and Technology (UST), Daejeon, Republic of Korea 4 World Class Institute, Anticancer Agents Research Center, Korea Research Institute of Bioscience and Biotechnology, Ochang, Cheongwon, Republic of Korea * These authors contributed equally to this work Correspondence to: Sun Chul Kang, email: sckang@daegu.ac.kr Hee Gu Lee, email: hglee@kribb.re.kr Keywords: apoptosis; autophagy; colorectal cancer; multidrug resistance; vitexin Received: October 02, 2017 Accepted: November 15, 2017 Published: December 04, 2017 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 DR ), 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 DR cells and showed cytotoxic effect in HCT-116 DR 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, in vivo experiments showed that vitexin induced apoptosis and suppressed tumor growth in HCT-116 DR 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.