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.
Highlights
Melanoma is one common skin cancer [1,2,3,4,5]
Cultured WM-115 human melanoma cells were treated with the liposomal C6
Liposomal C6-induced cytotoxicity (Fig 4C) and apoptosis (Fig 4D) were attenuated in phosphatase 1 (PP1) shRNA-expressing WM-115 cells. These results suggest that liposomal C6 activates PP1 to inhibit Akt-mammalian target of rapamycin (mTOR), causing melanoma cell growth inhibition and apoptosis
Summary
Melanoma is one common skin cancer [1,2,3,4,5]. It is characterized by rapid disease progression and early invasion/metastasis to other organs [6]. It is estimated that metastatic or recurrent melanoma causes over 8000 deaths each year [5]. Melanoma is resistant to almost all traditional chemotherapy agents [1,2,3,4]. Dacarbazine and temozolomide (TMZ) are routinely prescribed for melanoma chemotherapy. It is urgent to explore novel and more potent anti-melanoma agents
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