title: Stellettin A induces endoplasmic reticulum stress in murine B16 melanoma cells.
abstract: Isomalabaricanes are a small class of rearranged triterpenoids obtained from marine sponges. Most of these are cytotoxic to tumor cells, but the underlying mechanism is not clear. In this study, it was demonstrated that stellettin A (1), obtained from Geodia japonica, inhibited the growth of B16F10 murine melanoma cells by the induction of endoplasmic reticulum stress and accumulation of unfolded proteins. Immunoblotting analysis revealed abnormal glycosylation patterns of two melanoma marker proteins, tyrosinase and tyrosinase-related protein 1, and the retention of these proteins in the endoplasmic reticulum. Compound 1 induced the upregulation of the unfolded protein chaperone, glucose-regulated protein 78, in a dose-dependent manner. Increase of autophagosome-associated protein light chain 3 (LC3) in a membrane-bound form (LC3II) and its immunofluorescence co-localization with tyrosinase suggest the possible removal of deglycosylated and unfolded proteins by autophagy of the cells. There was no change in either the expression of the apoptosis marker protein Bcl-2 or the appearance of apoptotic nuclei in 1-treated cells. Taken together, 1 is an endoplasmic reticulum stressor that inhibits the growth of B16 melanoma cells by induction of abnormal protein glycosylation and autophagy.
authors.affiliation: School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong, People's Republic of China. ken-liu@cuhk.edu.hk
authors.forename: Wing Keung
authors.initials: WK
authors.lastname: Liu
authors.forename: Yick Hin
authors.initials: YH
authors.lastname: Ling
authors.forename: Florence W K
authors.initials: FW
authors.lastname: Cheung
authors.forename: Chun-Tao
authors.initials: CT
authors.lastname: Che
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001343:Autophagy / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects*; D047231:Geodia / Q000737:chemistry*; D006031:Glycosylation / Q000187:drug effects; D006801:Humans; D008386:Marine Biology; D008546:Melanoma, Experimental / Q000378:metabolism; D051379:Mice; D015394:Molecular Structure; D014315:Triterpenes / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D014315:Triterpenes; C091312:stellettin A