title: Apoptosis of human breast carcinoma cells in the presence of disialosyl gangliosides: II. Treatment of SKBR3 cells with GD3 and GD1b gangliosides.
abstract: Apoptosis, or programmed cell death, plays an important role in many physiological and diseased conditions. Induction of apoptosis in cancer cells has been monitored during the cells' progression to apoptosis by anti-cancer drugs and inhibitors of the cell surface glycolipids, gangliosides and SA-Le(x) biosyntheses [Basu, S (1991) Glycobiology, 1, 469-475; and ibid, 427-435] in animal tissues and human carcinoma cells, respectively. Induction of apoptosis in cancer cells by cell surface glycolipids in the human breast cancer (SKBR3) cells is the aim in this study. We have employed the disialosyl gangliosides (GD3 and GD1b) to initiate apoptosis in SKBR3 cells grown in culture in the presence of (14)C-L-Serine. At lower concentrations (0-20 microM) of exogenously added non-radioactive GD3, GD1b, or bovine ganglioside mixture (GM1:GD1a:GD1b:GT1a 2:4:4:2), the incorporation of radioactivity in both (14)C-sphingolipid and (14)C-ceramide was higher. However, at higher concentrations (20-100 microM), wherein apoptosis occurred in high frequency, the (14)C-incorporation decreased in both GSLs and ceramide. Apoptosis induction was monitored by the concomitant appearance of caspase-3 activation and the binding of a fluorescent dye PSS-380 to the outer leaflet of phosphatidyl-serine. These results indicated that, in addition to many unknown cell surface glycoconjugates GD3 or GD1b (disialosyl ganglioside) could play an important role in the regulation of breast carcinoma cell death.
authors.affiliation: Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, IN 46556, USA.
authors.forename: Rui
authors.initials: R
authors.lastname: Ma
authors.forename: Atanas
authors.initials: A
authors.lastname: Koulov
authors.forename: Christopher
authors.initials: C
authors.lastname: Moulton
authors.forename: Manju
authors.initials: M
authors.lastname: Basu
authors.forename: Sipra
authors.initials: S
authors.lastname: Banerjee
authors.forename: Holly
authors.initials: H
authors.lastname: Goodson
authors.forename: Subhash
authors.initials: S
authors.lastname: Basu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002417:Cattle; D045744:Cell Line, Tumor; D004789:Enzyme Activation / Q000187:drug effects; D005732:Gangliosides / Q000096:biosynthesis / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D008856:Microscopy, Fluorescence; D010718:Phosphatidylserines / Q000737:chemistry / Q000378:metabolism; D012694:Serine / Q000737:chemistry / Q000378:metabolism; D013107:Sphingolipids / Q000737:chemistry / Q000378:metabolism
chemical_list: D005732:Gangliosides; D010718:Phosphatidylserines; D013107:Sphingolipids; C025447:sialogangliosides; C033851:ganglioside, GD1b; D012694:Serine; C026226:ganglioside, GD3; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases