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Oleanolic acid induces protective autophagy in cancer cells through the JNK and mTOR pathways

文献类型： 外文期刊

作者： Liu, Jia 1 ; Zheng, Lanhong 2 ; Zhong, Jiateng 5 ; Wu, Ning 1 ; Liu, Ge 1 ; Lin, Xiukun 1 ;

作者机构： 1.Chinese Acad Sci, Inst Oceanol, Qingdao 266071, Shandong, Peoples R China

2.Chinese Acad Fishery Sci, Yellow Sea Fisheries Res Inst, Qingdao 266071, Shandong, Peoples R China

3.Univ Chinese Acad Sci, Grad Sch, Beijing 100049, Peoples R China

4.Capital Med Univ, Dept Pharmacol, Beijing 100069, Peoples R China

5.Jilin Univ, Norman Bethune Coll Med, Dept Pathophysiol, Changchun 130021, Jilin, Peoples R China

关键词： oleanolic acid;autophagy;cancer;mammalian target of rapamycin;c-jun N-terminal kinase

期刊名称：ONCOLOGY REPORTS （ 影响因子：3.906； 五年影响因子：4.011 ）

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收录情况： SCI

摘要： Autophagy is a biological process that eliminates damaged or excessive proteins and is utilized by various types of cells to maintain cellular homeostasis. Autophagy also occurs in cancer cells and exerts anti-survival or pro-survival effects depending on stimuli, nutrient and context. Oleanolic acid (OA), a widely spread natural compound, induces apoptosis in a range of cancer cells. However, some tumor cell lines are resistant to the pro-apoptotic effect of OA, and the mechanism remains unknown. In the present study, we found that OA induced autophagic event in cancer cells in a dose- and time-dependent manner, evidenced by an increased ratio between LC3-II and LC3-I and frequent granulation of LC3 proteins in OA-stimulated tumor cell lines. Inhibition of autophagy potentiated the pro-apoptotic activity of OA on cancer cells. Furthermore, the JNK and mTOR signaling pathways were found to be affected by OA treatment. Interfering with INK and mTOR abolished OA-induced autophagy and sensitized cancer cells to apoptosis. Collectively, we showed that OA was able to initiate protective autophagy, which compromised the antitumor activity of OA on cancer cells. Blocking autophagy may be a promising strategy to enhance the tumor suppressor activity of OA.

  • 相关文献

[1]p38 MAPK Signaling Mediates Mitochondrial Apoptosis in Cancer Cells Induced by Oleanolic Acid. Liu, Jia,Wu, Ning,Liu, Ge,Lin, Xiu-Kun,Zheng, Lan-Hong,Ma, Lei-Na,Liu, Ge,Lin, Xiu-Kun,Zhong, Jia-Teng. 2014

[2]Oleanolic acid inhibits proliferation and invasiveness of Kras-transformed cells via autophagy. Liu, Jia,Zheng, Lanhong,Liu, Jia,Wu, Ning,Liu, Ge,Lin, Xiukun,Ma, Leina,Wang, Bin,Zhao, Youguang,Lin, Xiukun.

[3]ERK inhibition sensitizes cancer cells to oleanolic acid-induced apoptosis through ERK/Nrf2/ROS pathway. Liu, Jia,Ma, Leina,Chen, Xiao,Wang, Jianxun,Yu, Tao,Gong, Ying,Ma, Aiguo,Liang, Hui,Ma, Leina,Zheng, Lanhong. 2016

[4]Oleanolic Acid Induces Metabolic Adaptation in Cancer Cells by Activating the AMP-Activated Protein Kinase Pathway. Liu, Jia,Wu, Ning,Liu, Ge,Lin, Xiukun,Zheng, Lanhong,Liu, Jia,Liu, Ge,Ma, Leina,Zhong, Jiateng,Lin, Xiukun.

[5]Patulin induces pro-survival functions via autophagy inhibition and p62 accumulation. Guo, X.,Dong, Y.,Yin, S.,Zhao, C.,Huo, Y.,Hu, H.,Guo, X.,Fan, L.. 2013

[6]Comparative study of two immunity-related GTPase genes in Chinese soft-shell turtle reveals their molecular characteristics and functional activity in immune defense. Shi, Yan,Hu, Sufei,Ding, Tie,Zhao, Zhe,Shi, Yan,Shen, Sixian,Hong, Xiaoyou,Chen, Chen,Zhu, Xinping. 2018

[7]Autophagy induced by infectious hematopoietic necrosis virus inhibits intracellular viral replication and extracellular viral yields in epithelioma papulosum cyprini cell line. Zhao, Jing-Zhuang,Xu, Li-Ming,Liu, Miao,Yin, Jia-Sheng,Liu, Hong-Bai,Lu, Tong-Yan,Zhang, Zhen-yu.

[8]Effect of follicle cell autophagy on gonadal development of triploid female rainbow trout (Oncorhynchus mykiss). Huang, Tianqing,Sun, Huizhi,Wang, Yanna,Wang, Xingran,Han, Ying,Xu, Gefeng. 2018

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