Induction of apoptosis by dideoxypetrosynol A, a polyacetylene from the sponge Petrosia sp., in human skin melanoma cells.
Dideoxypetrosynol A, a polyacetylene from the sponge Petrosia sp., is known to exhibit significant selective cytotoxicity against several human tumor cell lines. In the present study, we investigated the possible mechanisms by which dideoxypetrosynol A exerts its anti-proliferative action in cultured human SK-MEL-2 skin melanoma cells. Exposure of SK-MEL-2 cells to dideoxypetrosynol A resulted in growth inhibition and induction of apoptosis in a dose-dependent manner as measured by MTT assay, fluorescent microscopy and flow cytometry analysis. The increase in apoptosis was associated with a dose-dependent up-regulation in proapoptotic Bax expression and down-regulation of anti-apoptotic Bcl-2. Apoptosis-inducing concentrations of dideoxypetrosynol A induced caspase-3 and caspase-9 activation accompanied by proteolytic degradation of poly(ADP-ribose)-polymerase and selective down-regulation of cIAP-1. Taken together, these findings provide important new insights into the possible molecular mechanisms of the anti-cancer activity of dideoxypetrosynol A.
Choi
Hye Joung
HJ
Department of Biochemistry, Dongeui University College of Oriental Medicineand Biomedical Research Center of Oriental Medicine, Busan 614-052, Korea. choiyh@deu.ac.kr
Bae
Song-Ja
SJ
Kim
Nam Deuk
ND
Jung
Jee H
JH
Choi
Yung Hyun
YH
D000480:Alkynes / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D015536:Down-Regulation / Q000187:drug effects; D004789:Enzyme Activation; D005233:Fatty Alcohols / Q000737:chemistry / Q000494:pharmacology*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D008545:Melanoma / Q000473:pathology*; D015394:Molecular Structure; D047130:Petrosia / Q000737:chemistry*; D053279:Polyynes; D011506:Proteins / Q000145:classification / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D012878:Skin Neoplasms / Q000473:pathology*; D051028:bcl-2-Associated X Protein
D000480:Alkynes; C494826:BAX protein, human; D005233:Fatty Alcohols; D051034:Inhibitor of Apoptosis Proteins; D011506:Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; C499970:dideoxypetrosynol A; D053279:Polyynes; D020169:Caspases