학술논문
The Nedd8-activating enzyme inhibitor MLN4924 suppresses colon cancer cell growth via triggering autophagy
이용수 2
- 영문명
- The Nedd8-activating enzyme inhibitor MLN4924 suppresses colon cancer cell growth via triggering autophagy
- 발행기관
- 대한생리학회-대한약리학회
- 저자명
- Yongzhu Lv Bing Li Kunna Han Yang Xiao Xianjun Yu Yong Ma Zhan Jiao Jianjun Gao
- 간행물 정보
- 『The Korean Journal of Physiology & Pharmacology』제22권 제6호, 617~625쪽, 전체 9쪽
- 주제분류
- 의약학 > 의학일반
- 파일형태
- 발행일자
- 2018.11.30
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국문 초록
영문 초록
Neddylation is a post-translational protein modification process. MLN4924 is a newly discovered pharmaceutical neddylation inhibitor that suppresses cancer growth with several cancer types. In our study, we first investigated the effect of MLN4924 on colon cancer cells (HCT116 and HT29). MLN4924 significantly inhibited the neddylation of cullin-1 and colon cancer cell growth in a time and dose-dependent manner. MLN4924 induced G2/M cell cycle arrest and apoptosis in HCT116 and HT29 cells. Moreover, MLN4924 also triggered autophagy in HCT116 and HT29 cells via suppressing the PI3K/AKT/mTOR pathway. Inhibiting autophagy by autophagy inhibitor 3-MA or ATG5 knockdown reversed the function of MLN4924 in suppressing colon cancer cell growth and cell death. Interestingly, MLN4924 suppresses colon cell growth in a xenograft model. Together, our finding revealed that blocking neddylation is an attractive colon cancer therapy strategy, and autophagy might act as a novel anti-cancer mechanism for the treatment of colon cancer by MLN4924.
목차
INTRODUCTION
METHODS
RESULTS
DISCUSSION
ACKNOWLEDGEMENTS
CONFLICTS OF INTEREST
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