P-215 - Induction of apoptosis by 7,8-dihydroxyflavone in human colon cancer HCT-116 cells through activation of p53 and AMPK signaling pathways

Date 04 July 2015
Event WorldGI 2015
Session Posters
Topics Basic Science
Colon Cancer
Presenter Y.H. Yoo
Citation Annals of Oncology (2015) 26 (suppl_4): 1-100. 10.1093/annonc/mdv233
Authors Y.H. Yoo1, C. Park2, M.H. Han1, S.H. Hong1, Y.H. Choi3
  • 1Dong-A University College of Medicine and Mitochondria Hub Regulation Center, Busan/KR
  • 2Dongeui University College of Natural Sciences and Human Ecology, Busan/KR
  • 3Dongeui University, Busan/KR

Abstract

Introduction

7,8-dihydroxyflavone (7,8-DHF) is a member of the flavonoid family of phytochemicals, which are abundant in fruits and vegetables. 7,8-DHF has been shown to possess anti-oxidative, anti-inflammatory and anti-tumor properties, but the anti-tumor mechanisms are not completely understood. In this study, we investigated the mechanisms of 7,8-DHF on the induction of apoptosis using human colon cancer HCT-116 cells.

Methods

Cytotoxicity was evaluated by MTT assay. Apoptosis was detected using DAPI staining, agarose gel electrophoresis and flow cytometry. The protein levels were determined by Western blot analysis. Caspases activities were measured using a colorimetric assay.

Results

Exposure of HCT-116 cells to 7,8-DHF resulted in a concentration-dependent growth inhibition and induction of apoptosis, which was associated with the proteolytic activation of caspases and degradation of poly(ADP-ribose) polymerase protein. Induction of apoptosis by 7,8-DHF was also accompanied by modulation of Bcl-2 family and inhibitor of apoptosis protein family proteins expression. In addition, 7,8-DHF markedly increased the phosphorylation of tumor suppressor p53 and AMP-activated protein kinase (AMPK); however, pretreatment p53-specific inhibitor, pifithrin-α, and AMPK-specific inhibitor, compound C, significantly decreased growth inhibition and apoptosis by 7,8-DHF.

Conclusion

These findings revealed that 7,8-DHF possesses antitumoral activity on human colon cancer cells by manipulating p53 and AMPK signaling, suggesting that 7,8-DHF may be beneficial as colon cancer treatments. [This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT & Future Planning (2014R1A1A1008460 & 2014 001483)