title: Oleanolic acid inhibits proliferation and invasiveness of Kras-transformed cells via autophagy.
abstract: 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.
authors.affiliation: College of Medicine, Qingdao University, Qingdao 266021, China; Institutes of Oceanology, Chinese Academy of Sciences, Qingdao 266071, China.
authors.forename: Jia
authors.initials: J
authors.lastname: Liu
authors.affiliation: Yellow Sea Fisheries Research Institute, Chinese Academy of Fishery Sciences, Qingdao 266071, China.
authors.forename: Lanhong
authors.initials: L
authors.lastname: Zheng
authors.affiliation: Department of Molecular Biology, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, China.
authors.forename: Leina
authors.initials: L
authors.lastname: Ma
authors.affiliation: Department of Gastroenterology, Institute of Surgery Research, Daping Hospital, Third Military Medical University, Chongqing 400042, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Wang
authors.affiliation: Department of Urology, General Hospital of Chengdu Military Area Command of Chinese PLA, Chengdu 610083, China.
authors.forename: Youguang
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Institutes of Oceanology, Chinese Academy of Sciences, Qingdao 266071, China.
authors.forename: Ning
authors.initials: N
authors.lastname: Wu
authors.affiliation: Institutes of Oceanology, Chinese Academy of Sciences, Qingdao 266071, China.
authors.forename: Ge
authors.initials: G
authors.lastname: Liu
authors.affiliation: Institutes of Oceanology, Chinese Academy of Sciences, Qingdao 266071, China; Capital Med. University, Dept. of Pharmacology, Beijing 100069, China. Electronic address: linxiukun@yahoo.com.
authors.forename: Xiukun
authors.initials: X
authors.lastname: Lin
mesh_terms: D000818:Animals; D001343:Autophagy / Q000187:drug effects*; D001940:Breast / Q000166:cytology / Q000378:metabolism; D001943:Breast Neoplasms / Q000517:prevention & control; D002461:Cell Line, Transformed; D049109:Cell Proliferation / Q000187:drug effects*; D005260:Female; D011905:Genes, ras; D006801:Humans; D051379:Mice; D009361:Neoplasm Invasiveness / Q000517:prevention & control*; D009828:Oleanolic Acid / Q000494:pharmacology*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D019893:Ribosomal Protein S6 Kinases / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism
chemical_list: D009828:Oleanolic Acid; C546842:MTOR protein, human; D051057:Proto-Oncogene Proteins c-akt; D019893:Ribosomal Protein S6 Kinases; D058570:TOR Serine-Threonine Kinases
keywords: Akt; Autophagy; Cancer prevention; Natural compounds; Oleanolic acid