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

Oncotarget 2018 Jan 4;9(3):3278-3291. Epub 2017 Dec 4.

Department of Biotechnology, Daegu University, Kyoungsan, Kyoungbook, Republic of Korea.

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.

Download full-text PDF

Source
http://dx.doi.org/10.18632/oncotarget.22890DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5790463PMC
January 2018
15 Reads

Publication Analysis

Top Keywords

vitexin treatment
12
vitexin
9
colorectal cancer
8
cancer cells
8
multi-drug resistant
8
hct-116 cells
8
induced apoptosis
8
cell hct-116
8
vitexin induced
8
cells
5
cancer
5
hct-116
5
cytotoxic hct-116
4
activity hct-116
4
cells cytotoxic
4
cells inhibiting
4
inhibiting autophagy
4
autophagy inducing
4
additionally vitexin
4
treatment caused
4

Similar Publications