title: Huaier Extract Induces Autophagic Cell Death by Inhibiting the mTOR/S6K Pathway in Breast Cancer Cells.
abstract: Huaier extract is attracting increased attention due to its biological activities, including antitumor, anti-parasite and immunomodulatory effects. Here, we investigated the role of autophagy in Huaier-induced cytotoxicity in MDA-MB-231, MDA-MB-468 and MCF7 breast cancer cells. Huaier treatment inhibited cell viability in all three cell lines and induced various large membranous vacuoles in the cytoplasm. In addition, electron microscopy, MDC staining, accumulated expression of autophagy markers and flow cytometry revealed that Huaier extract triggered autophagy. Inhibition of autophagy attenuated Huaier-induced cell death. Furthermore, Huaier extract inhibited the mammalian target of the rapamycin (mTOR)/S6K pathway in breast cancer cells. After implanting MDA-MB-231 cells subcutaneously into the right flank of BALB/c nu/nu mice, Huaier extract induced autophagy and effectively inhibited xenograft tumor growth. This study is the first to show that Huaier-induced cytotoxicity is partially mediated through autophagic cell death in breast cancer cells through suppression of the mTOR/S6K pathway.
authors.affiliation: Department of Breast Surgery, Qilu Hospital, Shandong University, Jinan, Shandong, P.R. China.
authors.forename: Xiaolong
authors.initials: X
authors.lastname: Wang
authors.affiliation: School of Medicine, Shandong University, Jinan, Shandong, P.R. China.
authors.forename: Wenwen
authors.initials: W
authors.lastname: Qi
authors.affiliation: School of Medicine, Shandong University, Jinan, Shandong, P.R. China.
authors.forename: Yaming
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Breast Surgery, Qilu Hospital, Shandong University, Jinan, Shandong, P.R. China.
authors.forename: Ning
authors.initials: N
authors.lastname: Zhang
authors.affiliation: Department of Breast Surgery, Qilu Hospital, Shandong University, Jinan, Shandong, P.R. China.
authors.forename: Lun
authors.initials: L
authors.lastname: Dong
authors.affiliation: Department of Breast Surgery, Qilu Hospital, Shandong University, Jinan, Shandong, P.R. China.
authors.forename: Mingjuan
authors.initials: M
authors.lastname: Sun
authors.affiliation: Department of Breast Surgery, Qilu Hospital, Shandong University, Jinan, Shandong, P.R. China.
authors.forename: Jinjing
authors.initials: J
authors.lastname: Cun
authors.affiliation: Qilu Hospital, Shandong University, Jinan, Shandong, P.R. China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: School of Medicine, Shandong University, Jinan, Shandong, P.R. China.
authors.forename: Shangge
authors.initials: S
authors.lastname: Lv
authors.affiliation: Department of Breast Surgery, Qilu Hospital, Shandong University, Jinan, Shandong, P.R. China; Department of Pathology Tissue Bank, Qilu Hospital, Shandong University, Jinan, Shandong, P.R. China.
authors.forename: Qifeng
authors.initials: Q
authors.lastname: Yang
mesh_terms: D000818:Animals; D017209:Apoptosis; D001343:Autophagy; D001688:Biological Products / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology*; D001952:Bridged-Ring Compounds / Q000494:pharmacology*; D045744:Cell Line, Tumor; D004354:Drug Screening Assays, Antitumor; D004365:Drugs, Chinese Herbal; D005260:Female; D006801:Humans; D020287:In Situ Nick-End Labeling; D061986:MCF-7 Cells; D051379:Mice; D008807:Mice, Inbred BALB C; D009368:Neoplasm Transplantation; D034741:RNA, Small Interfering / Q000378:metabolism; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000037:antagonists & inhibitors / Q000378:metabolism*; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D055454:Trametes / Q000737:chemistry*
chemical_list: D001688:Biological Products; D001952:Bridged-Ring Compounds; D004365:Drugs, Chinese Herbal; D034741:RNA, Small Interfering; C546842:MTOR protein, human; C546843:mTOR protein, mouse; D038762:Ribosomal Protein S6 Kinases, 70-kDa; D058570:TOR Serine-Threonine Kinases; C448901:ribosomal protein S6 kinase, 70kD, polypeptide 1