title: Autophagy induction by silibinin positively contributes to its anti-metastatic capacity via AMPK/mTOR pathway in renal cell carcinoma.
abstract: Silibinin, a dietary cancer chemopreventive flavonoid from the seeds of milk thistle, has been reported to exhibit anti-metastatic effects on renal cell carcinoma (RCC), but the mechanism underlying this phenomenon is not fully understood. The present study aimed at examining the potential role of autophagy in regulating silibinin-induced anti-metastatic effects on RCC cells. Using RCC ACHN and 786-O cells as a model system in vitro, we found that silibinin treatment increased the expression of LC3-II, resulted in the formation of autophagolysosome vacuoles, and caused a punctate fluorescence pattern with the monomeric red fluorescence protein-enhanced green fluorescence protein-LC3 (mRFP-EGFP-LC3) protein, which all are markers for cellular autophagy. Autophagy flux was induced by silibinin in RCC cells, as determined by LC3 turnover assay. Mechanically, the adenosine 5'-monophosphate activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR) pathway was identified as involved in regulation of silibinin-induced autophagy. Furthermore, autophagy induction was demonstrated to positively contribute to silibinin-induced anti-metastatic effects on RCC cells in vitro. Activation of autophagy enhanced silibinin-induced inhibition of migration and invasion of RCC cells, while inhibition of autophagy attenuated it. These findings thus provide new information about the potential link between autophagy and metastasis inhibition induced by silibinin, and the induction of autophagy may shed some light into future treatment strategies for metastatic RCC.
authors.affiliation: Department of Urology, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China. tctx880315@gmail.com.
authors.forename: Feng
authors.initials: F
authors.lastname: Li
authors.affiliation: Department of Urology, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China. mazhenkun.8@stu.xjtu.edu.cn.
authors.forename: Zhenkun
authors.initials: Z
authors.lastname: Ma
authors.affiliation: Department of Urology, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China. guanzhenfeng@163.com.
authors.forename: Zhenfeng
authors.initials: Z
authors.lastname: Guan
authors.affiliation: Department of Urology, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China. xdwyd@stu.xjtu.edu.cn.
authors.forename: Yule
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Urology, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China. yidaiwujin@126.com.
authors.forename: Kaijie
authors.initials: K
authors.lastname: Wu
authors.affiliation: Department of Urology, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China. guopeng661@mail.xjtu.edu.cn.
authors.forename: Peng
authors.initials: P
authors.lastname: Guo
authors.affiliation: Key Laboratory of Environment and Genes Related to Diseases, Ministry of Education of China, Xi'an 710061, China. wangxinyang0929@163.com.
authors.forename: Xinyang
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Urology, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China. dalinhexjtu1@gmail.com.|Key Laboratory of Environment and Genes Related to Diseases, Ministry of Education of China, Xi'an 710061, China. dalinhexjtu1@gmail.com.
authors.forename: Dalin
authors.initials: D
authors.lastname: He
authors.affiliation: Department of Urology, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China. zengjin1984@gmail.com.
authors.forename: Jin
authors.initials: J
authors.lastname: Zeng
mesh_terms: D000263:Adenylate Kinase / Q000378:metabolism; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001343:Autophagy / Q000187:drug effects*; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000556:secondary; D045744:Cell Line, Tumor; D002465:Cell Movement; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000473:pathology; D015398:Signal Transduction; D000077385:Silybin; D012838:Silymarin / Q000494:pharmacology*; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D012838:Silymarin; D000077385:Silybin; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases; D000263:Adenylate Kinase