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Oleanolic acid inhibits proliferation and invasiveness of Kras-transformed cells via autophagy

文献类型： 外文期刊

作者： Liu, Jia 1 ; Zheng, Lanhong 2 ; Ma, Leina 4 ; Wang, Bin 5 ; Zhao, Youguang 6 ; Wu, Ning 3 ; Liu, Ge 3 ; Lin, Xiukun 3 ;

作者机构： 1.Qingdao Univ, Coll Med, Qingdao 266021, Peoples R China

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

3.Chinese Acad Sci, Inst Oceanol, Qingdao 266071, Peoples R China

4.Ocean Univ China, Sch Med & Pharm, Dept Mol Biol, Qingdao 266003, Peoples R China

5.Third Militaty Med Univ, Daping Hosp, Inst Surg Res, Dept Gastroenterol, Chongqing 400042, Peoples R China

6.Chinese PLA, Chengdu Mil Area Command, Gen Hosp, Dept Urol, Chengdu 610083, Peoples R China

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

关键词： Oleanolic acid;Autophagy;Akt;Cancer prevention;Natural compounds

期刊名称：JOURNAL OF NUTRITIONAL BIOCHEMISTRY （ 影响因子：6.048； 五年影响因子：6.114 ）

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收录情况： SCI

摘要： Oleanolic acid (OA) has been widely studied because of its pleiotropic therapeutic and preventive effect on various diseases. However, the mechanisms of OA's action are still not clear yet, especially its suppressing effect on transformed cells. In this work, we found that OA induced autophagy in normal tissue-derived cells without cytotoxicity. OA-induced autophagy was shown to decrease the proliferation of KRAS-transformed normal cells and to impair their invasion and anchorage-independent growth. Interrupting autophagy rescued OA's effect on the transformed cells. Mouse model experiments also demonstrated that OA suppressed the growth of KRAS-transformed breast epithelial cell MCF10A-derived tumor xenograft by inducing autophagy. Finally, we identified that OA induced autophagy in normal cells by inhibiting the activation of Akt/mTOR/S6K signaling. In conclusions, we found that OA treatment permitted normal cells to undergo autophagy. The induced autophagy was required for OA to prevent or delay the growth of transformed normal cells. (C) 2014 Published by Elsevier Inc.

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[1]Oleanolic acid induces protective autophagy in cancer cells through the JNK and mTOR pathways. Liu, Jia,Wu, Ning,Liu, Ge,Lin, Xiukun,Zheng, Lanhong,Liu, Jia,Liu, Ge,Lin, Xiukun,Zhong, Jiateng.

[2]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.

[3]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

[4]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

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