title: Myriocin, a serine palmitoyltransferase inhibitor, suppresses tumor growth in a murine melanoma model by inhibiting de novo sphingolipid synthesis.
abstract: Advanced melanoma is the most virulent form of cancer and has a poor prognosis. In a previous study, myriocin, an inhibitor of serine palmitoyltransferase, was found to suppress melanoma cell proliferation by cell cycle arrest at the G 2/M phase through decreased sphingolipid levels and increased p53 and p21 (waf1/cip1)  expression. ( 1)  In the present study, myriocin (1 mg/kg, every other day for 3 weeks) was administered intradermally or intraperitoneally to melanoma mice. Tumor formation was significantly inhibited by intradermal and intraperitoneal administration of myriocin. The expression of Cdc25C, Cdc2 and cyclin B1 was decreased in tumor tissues from myriocin-treated mice, while the expression of p53 and p21 (waf1/cip1)  was increased compared with that of the controls. The levels of sphingolipids in serum, liver and tumor tissue from myriocin-treated mice were decreased compared with those of controls. The decreased levels of sphingolipids in serum and liver of melanoma mice treated with myriocin suggests that myriocin may be accessible to tumor tissues of advanced melanoma. Taken together, the suppression of sphingolipid synthesis by myriocin inhibits the expression of Cdc25C or activates the expression of p53 and p21 (waf1/cip1) . This is followed by Cdc2 and cyclin B1 inhibition which results in the suppression of tumor growth.
authors.affiliation: College of Pharmacy and Medical Research Center; Chungbuk National University, Cheongju, Korea.
authors.forename: Youn-Sun
authors.initials: YS
authors.lastname: Lee
authors.forename: Kyeong-Mi
authors.initials: KM
authors.lastname: Choi
authors.forename: Seunghyun
authors.initials: S
authors.lastname: Lee
authors.forename: Dong-Mi
authors.initials: DM
authors.lastname: Sin
authors.forename: Yong
authors.initials: Y
authors.lastname: Lim
authors.forename: Yong-Moon
authors.initials: YM
authors.lastname: Lee
authors.forename: Jin-Tae
authors.initials: JT
authors.lastname: Hong
authors.forename: Yeo-Pyo
authors.initials: YP
authors.lastname: Yun
authors.forename: Hwan-Soo
authors.initials: HS
authors.lastname: Yoo
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D004195:Disease Models, Animal; D005229:Fatty Acids, Monounsaturated / Q000008:administration & dosage / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects; D008546:Melanoma, Experimental / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008954:Models, Biological; D051102:Serine C-Palmitoyltransferase / Q000037:antagonists & inhibitors*; D013107:Sphingolipids / Q000096:biosynthesis*
chemical_list: D000970:Antineoplastic Agents; D018797:Cell Cycle Proteins; D005229:Fatty Acids, Monounsaturated; D013107:Sphingolipids; D051102:Serine C-Palmitoyltransferase; C001996:thermozymocidin