title: Liposomal C6 Ceramide Activates Protein Phosphatase 1 to Inhibit Melanoma Cells.
abstract: Melanoma is one common skin cancer. In the present study, the potential anti-melanoma activity by a liposomal C6 ceramide was tested in vitro. We showed that the liposomal C6 (ceramide) was cytotoxic and anti-proliferative against a panel of human melanoma cell lines (SK-Mel2, WM-266.4 and A-375 and WM-115). In addition, liposomal C6 induced caspase-dependent apoptotic death in the melanoma cells. Reversely, its cytotoxicity was attenuated by several caspase inhibitors. Intriguingly, liposomal C6 was non-cytotoxic to B10BR mouse melanocytes and primary human melanocytes. Molecularly, liposomal C6 activated protein phosphatase 1 (PP1) to inactivate Akt-mammalian target of rapamycin (mTOR) signaling in melanoma cells. On the other hand, PP1 shRNA knockdown or exogenous expression of constitutively activate Akt1 (CA-Akt1) restored Akt-mTOR activation and significantly attenuated liposomal C6-mediated cytotoxicity and apoptosis in melanoma cells. Our results suggest that liposomal C6 activates PP1 to inhibit melanoma cells.
authors.affiliation: Department of Plastic and Reconstructive Surgery, the Second Affiliated Hospital of Zhejiang University, College of Medicine, Hangzhou, 310009, China.
authors.forename: Fangzhen
authors.initials: F
authors.lastname: Jiang
authors.affiliation: Department of Ophthalmology, the Second Affiliated Hospital of Zhejiang University, College of Medicine, Hangzhou, 310009, China.
authors.forename: Kai
authors.initials: K
authors.lastname: Jin
authors.affiliation: Department of Ophthalmology, the Second Affiliated Hospital of Zhejiang University, College of Medicine, Hangzhou, 310009, China.
authors.forename: Shenyu
authors.initials: S
authors.lastname: Huang
authors.affiliation: Department of Plastic and Reconstructive Surgery, the Second Affiliated Hospital of Zhejiang University, College of Medicine, Hangzhou, 310009, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Bao
authors.affiliation: Department of Plastic and Reconstructive Surgery, the Second Affiliated Hospital of Zhejiang University, College of Medicine, Hangzhou, 310009, China.
authors.forename: Zheren
authors.initials: Z
authors.lastname: Shao
authors.affiliation: Department of Plastic and Reconstructive Surgery, the Second Affiliated Hospital of Zhejiang University, College of Medicine, Hangzhou, 310009, China.
authors.forename: Xueqing
authors.initials: X
authors.lastname: Hu
authors.affiliation: Department of Ophthalmology, the Second Affiliated Hospital of Zhejiang University, College of Medicine, Hangzhou, 310009, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Ye
mesh_terms: D045744:Cell Line, Tumor; D002518:Ceramides / Q000378:metabolism*; D004789:Enzyme Activation; D006801:Humans; D008081:Liposomes / Q000378:metabolism*; D008545:Melanoma / Q000473:pathology*; D054645:Protein Phosphatase 1 / Q000378:metabolism*
chemical_list: D002518:Ceramides; D008081:Liposomes; D054645:Protein Phosphatase 1