title: Cryptotanshinone induces melanoma cancer cells apoptosis via ROS-mitochondrial apoptotic pathway and impairs cell migration and invasion.
abstract: Melanoma is the most serious type of skin cancer because it is highly frequency of drug resistance and can spread earlier and more quickly than other skin cancers. The objective of this research was to investigate the anticancer effects of cryptotanshinone on human melanoma cells in vitro, and explored its mechanisms of action. Our results have shown that cryptotanshinone could inhibit cell proliferation in human melanoma cell lines A2058, A375, and A875 in a dose- and time-dependent manner. In addition, flow cytometry assay showed that cryptotanshinone inhibited the proliferation of human melanoma cell line A375 by blocking cell cycle progression in G2/M phase and inducing apoptosis in a concentration-dependent manner. Moreover, western blot analysis indicated that the occurrence of its apoptosis was associated with upregulation of cleaved caspases-3 and pro-apoptotic protein Bax while downregulation of anti-apoptotic protein Bcl-2. Meanwhile, cryptotanshinone could decrease the levels of reactive oxygen species (ROS). Furthermore, cryptotanshinone also blocked A375 cell migration and invasion in vitro which was associated with the downregulation with MMP-9. Taken together, these results suggested that cryptotanshinone might be a potential drug in human melanoma treatment by inhibiting proliferation, inducing apoptosis via ROS-mitochondrial apoptotic pathway and blocking cell migration and invasion.
authors.affiliation: Department of Gastroenterology, State Key Laboratory of Biotherapy/Collaborative Innovation Center for Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu, China.
authors.forename: Tinghong
authors.initials: T
authors.lastname: Ye
authors.affiliation: Department of Encephalopathy, The First Affiliated Hospital of Henan University of Traditional Chinese Medicine, Henan University of Traditional Chinese Medicine, Zhengzhou, China.
authors.forename: Shirui
authors.initials: S
authors.lastname: Zhu
authors.affiliation: Department of Gastroenterology, State Key Laboratory of Biotherapy/Collaborative Innovation Center for Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu, China.
authors.forename: Yongxia
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Department of Gastroenterology, State Key Laboratory of Biotherapy/Collaborative Innovation Center for Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu, China; College of Chemistry and Life Science, Chengdu Normal University, Chengdu, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Feng
authors.affiliation: Department of Gastroenterology, State Key Laboratory of Biotherapy/Collaborative Innovation Center for Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu, China; College of Chemistry and Life Science, Chengdu Normal University, Chengdu, China.
authors.forename: Bing
authors.initials: B
authors.lastname: He
authors.affiliation: Department of Gastroenterology, State Key Laboratory of Biotherapy/Collaborative Innovation Center for Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu, China.
authors.forename: Yiong
authors.initials: Y
authors.lastname: Xiong
authors.affiliation: Department of Gastroenterology, State Key Laboratory of Biotherapy/Collaborative Innovation Center for Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu, China. Electronic address: lifengzhao@scu.edu.cn.
authors.forename: Lifeng
authors.initials: L
authors.lastname: Zhao
authors.affiliation: Department of Gastroenterology, State Key Laboratory of Biotherapy/Collaborative Innovation Center for Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu, China. Electronic address: yiwenzhang@scu.edu.cn.
authors.forename: Yiwen
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Gastroenterology, State Key Laboratory of Biotherapy/Collaborative Innovation Center for Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu, China.
authors.forename: Luoting
authors.initials: L
authors.lastname: Yu
authors.affiliation: Department of Gastroenterology, State Key Laboratory of Biotherapy/Collaborative Innovation Center for Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu, China.
authors.forename: Li
authors.initials: L
authors.lastname: Yang
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D048430:Cell Shape / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D059565:G2 Phase Cell Cycle Checkpoints / Q000187:drug effects; D006801:Humans; D008545:Melanoma / Q000378:metabolism* / Q000473:pathology*; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D010616:Phenanthrenes / Q000737:chemistry / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D012878:Skin Neoplasms / Q000378:metabolism / Q000473:pathology; D014410:Tumor Stem Cell Assay
chemical_list: D010616:Phenanthrenes; D017382:Reactive Oxygen Species; C037886:cryptotanshinone
keywords: Apoptosis; Cell cycle; Cryptotanshinone; Melanoma; Migration and invasion