title: n-3 polyunsaturated fatty acids abrogate mTORC1/2 signaling and inhibit adrenocortical carcinoma growth in vitro and in vivo.
abstract: n-3 polyunsaturated fatty acids (PUFAs) are essential for human health and have been reported to reduce the risk of cancer, inhibit the growth of various types of tumors both in vitro and in vivo, and affect adrenal function. However, their effects on adrenocortical carcinoma (ACC) are not known. In the present study, we demonstrated that docosahexenoic acid (DHA) inhibited ACC cell proliferation, colony formation and cell cycle progression, and promoted apoptosis. In addition, ectopic expression of fat-1, a desaturase that converts n-6 to n-3 PUFAs endogenously, also inhibited ACC cell proliferation. Moreover, supplementing n-3 PUFAs in the diet efficiently prevented ACC cell growth in xenograft models. Notably, implanted ACC cells were unable to grow in fat-1 transgenic severe combined immune deficiency mice. Further study revealed that exogenous and endogenous n-3 PUFAs efficiently suppressed both mTOR complex 1 (mTORC1) and mTORC2 signaling in ACC in vitro and in vivo. Taken together, our findings provide comprehensive preclinical evidence that n-3 PUFAs efficiently prevent ACC growth by inhibiting mTORC1/2, which may have important implications in the treatment of ACC.
authors.affiliation: Department of Urology, Guangzhou General Hospital of Guangzhou Military Command, Guangzhou 510010, P.R. China.
authors.forename: Jun
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Cell Biology, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, P.R. China.
authors.forename: Meinian
authors.initials: M
authors.lastname: Xu
authors.affiliation: Department of Urology, Guangzhou General Hospital of Guangzhou Military Command, Guangzhou 510010, P.R. China.
authors.forename: Yongbin
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Department of Cell Biology, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, P.R. China.
authors.forename: Chunping
authors.initials: C
authors.lastname: Ao
authors.affiliation: Department of Cell Biology, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, P.R. China.
authors.forename: Yukun
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Department of Cell Biology, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, P.R. China.
authors.forename: Zhenguo
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Department of Urology, Guangzhou General Hospital of Guangzhou Military Command, Guangzhou 510010, P.R. China.
authors.forename: Bangqi
authors.initials: B
authors.lastname: Wang
authors.affiliation: Department of Cell Biology, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, P.R. China.
authors.forename: Xiaochun
authors.initials: X
authors.lastname: Bai
authors.affiliation: Department of Cell Biology, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, P.R. China.
authors.forename: Ming
authors.initials: M
authors.lastname: Li
authors.affiliation: Department of Urology, Guangzhou General Hospital of Guangzhou Military Command, Guangzhou 510010, P.R. China.
authors.forename: Weilie
authors.initials: W
authors.lastname: Hu
mesh_terms: D000306:Adrenal Cortex Neoplasms / Q000188:drug therapy* / Q000473:pathology; D018268:Adrenocortical Carcinoma / Q000188:drug therapy* / Q000473:pathology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D004281:Docosahexaenoic Acids / Q000494:pharmacology*; D005260:Female; D006801:Humans; D000076222:Mechanistic Target of Rapamycin Complex 1; D000076225:Mechanistic Target of Rapamycin Complex 2; D051379:Mice; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D016513:Mice, SCID; D046912:Multiprotein Complexes / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
chemical_list: D046912:Multiprotein Complexes; D004281:Docosahexaenoic Acids; D000076222:Mechanistic Target of Rapamycin Complex 1; D000076225:Mechanistic Target of Rapamycin Complex 2; D058570:TOR Serine-Threonine Kinases