Geoditin A induces oxidative stress and apoptosis on human colon HT29 cells.
Geoditin A, an isomalabaricane triterpene isolated from the marine sponge Geodia japonica, has been demonstrated to dissipate mitochondrial membrane potential, activate caspase 3, decrease cytoplasmic proliferating cell nuclear antigen (PCNA), and induce apoptosis of leukemia cells, but the underlying mechanism remains unclear [1]. In this study, we found fragmentation of Golgi structure, suppression of transferrin receptor expression, production of oxidants, and DNA fragmentation in human colon cancer HT29 cells after treatment with geoditin A for 24 h. This apoptosis was not abrogated by chelation of intracellular iron with salicylaldehyde isonicotinoyl hydrazone (SIH), but suppressed by N-acetylcysteine (NAC), a thiol antioxidant and GSH precursor, indicating that the cytotoxic effect of geoditin A is likely mediated by a NAC-inhibitable oxidative stress. Our results provide a better understanding of the apoptotic properties and chemotherapeutical potential of this marine triterpene.
Cheung
Florence W K
FW
School of Chinese Medicine, Chinese University of Hong Kong, Shatin, NT, Hong Kong, China. Florence_cwk@hotmail.com
Li
Chunman
C
Che
Chun-Tao
CT
Liu
Bonnie P L
BP
Wang
Lijun
L
Liu
Wing-Keung
WK
D000111:Acetylcysteine / Q000494:pharmacology; D000230:Adenocarcinoma / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D000818:Animals; D000970:Antineoplastic Agents / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D053938:DNA Fragmentation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects; D004705:Endocytosis / Q000187:drug effects; D016166:Free Radical Scavengers / Q000494:pharmacology; D006056:Golgi Apparatus / Q000187:drug effects / Q000473:pathology; D019073:HT29 Cells; D006801:Humans; D020128:Inhibitory Concentration 50; D007502:Iron Chelating Agents / Q000494:pharmacology; D008387:Marine Toxins / Q000037:antagonists & inhibitors / Q000633:toxicity*; D016877:Oxidants / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D011990:Receptors, Transferrin / Q000378:metabolism; D012118:Resorcinols / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D014315:Triterpenes / Q000037:antagonists & inhibitors / Q000494:pharmacology*
D000970:Antineoplastic Agents; D016166:Free Radical Scavengers; D007502:Iron Chelating Agents; D008387:Marine Toxins; D016877:Oxidants; D011990:Receptors, Transferrin; D012118:Resorcinols; D014315:Triterpenes; C445692:geoditin A; D000111:Acetylcysteine