20(S)-Ginsenoside Rh2-induced apoptosis and protective autophagy in cervical cancer cells by inhibiting AMPK/mTOR pathway

被引:14
作者
Bian, Shuai [1 ]
Liu, Meichen [1 ]
Yang, Song [1 ]
Lu, Shuyan [1 ]
Wang, Siming [1 ]
Bai, Xueyuan [1 ]
Zhao, Daqing [1 ]
Wang, Jiawen [1 ]
机构
[1] Changchun Univ Chinese Med, Jilin Ginseng Acad, Changchun, Jilin, Peoples R China
基金
中国国家自然科学基金;
关键词
ginsenoside Rh2; protective autophagy; apoptosis; HeLa cells; cervical cancer; GINSENOSIDE RH2; ACTIVATION; GROWTH;
D O I
10.1093/bbb/zbab189
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
20(S)-Ginsenoside Rh2 (GRh2) has various biological activities including anticancer effects. However, no reports have investigated the connection between autophagy and apoptosis in HeLa cells treated with 20(S)-GRh2. In this study, we found that 20(S)-GRh2 suppressed proliferation and induced apoptosis in HeLa cells by activating the intrinsic apoptotic pathway and causing mitochondrial dysfunction. 20(S)-GRh2 enhanced cell autophagy through promoting the phosphorylation of AMPK, depressed the phosphorylation of AKT, and suppressed mTOR activity. Furthermore, treatment with the autophagy inhibitor 3-methyladenine (3-MA) enhanced 20(S)-GRh2-induced apoptosis, while the autophagy inducer rapamycin promoted cell survival. Moreover, the apoptosis inhibitor Z-VAD-FMK significantly restrained the apoptosis and autophagy induced by 20(S)-GRh2 in HeLa cells. We found that 20(S)-ginsenoside Rh2-induced protective autophagy promotes apoptosis of cervical cancer cells by inhibiting AMPK/mTOR pathway.
引用
收藏
页码:92 / 103
页数:12
相关论文
共 40 条
[1]   Fertility-Sparing Surgery in Early-Stage Cervical Cancer: Indications and Applications [J].
Abu-Rustum, Nadeem R. ;
Sonoda, Yukio .
JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK, 2010, 8 (12) :1435-1438
[2]   Functional role of ginseng-derived compounds in cancer [J].
Ahuja, Akash ;
Kim, Ji Hye ;
Kim, Jong-Hoon ;
Yi, Young-Su ;
Cho, Jae Youl .
JOURNAL OF GINSENG RESEARCH, 2018, 42 (03) :248-254
[3]   Regulation of reactive oxygen species generation in cell signaling [J].
Bae, Yun Soo ;
Oh, Hyunjin ;
Rhee, Sue Goo ;
Do Yoo, Young .
MOLECULES AND CELLS, 2011, 32 (06) :491-509
[4]   Apoptosis: A review of programmed cell death [J].
Elmore, Susan .
TOXICOLOGIC PATHOLOGY, 2007, 35 (04) :495-516
[5]   Ginsenoside Rk1 bioactivity: a systematic review [J].
Elshafay, Abdelrahman ;
Ngo Xuan Tinh ;
Salman, Samar ;
Shaheen, Yara Saber ;
Othman, Eman Bashir ;
Elhady, Mohamed Tamer ;
Kansakar, Aswin Ratna ;
Linh Tran ;
Le Van ;
Hirayama, Kenji ;
Nguyen Tien Huy .
PEERJ, 2017, 5
[6]   Role of p62 in the regulation of cell death induction [J].
Fan, Lihong ;
Yin, Shutao ;
Zhang, Enxiang ;
Hu, Hongbo .
APOPTOSIS, 2018, 23 (3-4) :187-193
[7]   Cancer incidence and mortality worldwide: Sources, methods and major patterns in GLOBOCAN 2012 [J].
Ferlay, Jacques ;
Soerjomataram, Isabelle ;
Dikshit, Rajesh ;
Eser, Sultan ;
Mathers, Colin ;
Rebelo, Marise ;
Parkin, Donald Maxwell ;
Forman, David ;
Bray, Freddie .
INTERNATIONAL JOURNAL OF CANCER, 2015, 136 (05) :E359-E386
[8]   Cervical cancer prevention and treatment research in Africa: a systematic review from a public health perspective [J].
Finocchario-Kessler, Sarah ;
Wexler, Catherine ;
Maloba, May ;
Mabachi, Natabhona ;
Ndikum-Moffor, Florence ;
Bukusi, Elizabeth .
BMC WOMENS HEALTH, 2016, 16
[9]   Human papillomavirus-associated cancers in patients with human immunodeficiency virus infection and acquired immunodeficiency syndrome [J].
Frisch, M ;
Biggar, IJ ;
Goedert, JJ .
JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE, 2000, 92 (18) :1500-1510
[10]  
Galluzzi L, 2008, CURR MOL MED, V8, P78