9-Oxo-(10E,12E)-octadecadienoic acid, a cytotoxic fatty acid ketodiene isolated from eggplant calyx, induces apoptosis in human ovarian cancer (HRA) cells.
9-Oxo-(10E,12E)-octadecadienoic acid (9-EE-KODE), which is isolated from the calyx of eggplants, exhibits cytotoxic activity against human ovarian cancer (HRA) cells. The aim of the present study is to clarify the action mechanism of 9-EE-KODE leading to cell death. After the treatment of 9-EE-KODE in HRA cells, we found intracellular DNA fragmentation, surface-exposure of phosphatidylserine in the outer cell membrane, and increased caspase-3/7 activities in the HRA cells. The dissipation of mitochondrial membrane potential, release of cytochrome c from mitochondria to cytosol, down-regulation of Bcl-2, and up-regulation of Bax levels were also found in 9-EE-KODE-treated cells in a dose-dependent manner. These results demonstrated that 9-EE-KODE induced apoptosis in HRA cells via the mitochondrial regulation pathway.
Department of Pharmacognosy, Graduate School of Pharmaceutical Science, Nagoya City University, 3-1 Tanabe-Dori, Mizuho-ku, Nagoya, 467-8603, Japan.
Baiyang
B
Zhao
Yutaka
Y
Tomoda
Hajime
H
Mizukami
Toshiaki
T
Makino
D000972:Antineoplastic Agents, Phytogenic / Q000302:isolation & purification / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D045304:Cytochromes c / Q000378:metabolism; D053938:DNA Fragmentation; D004354:Drug Screening Assays, Antitumor; D005260:Female; D035264:Flowers / Q000737:chemistry*; D006801:Humans; D008042:Linolenic Acids / Q000302:isolation & purification / Q000494:pharmacology*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000378:metabolism; D010051:Ovarian Neoplasms / Q000188:drug therapy*; D032323:Solanum melongena / Q000737:chemistry*
D000972:Antineoplastic Agents, Phytogenic; D008042:Linolenic Acids; C062143:9-oxo-10,12-octadecadienoic acid; D045304:Cytochromes c; C505407:CASP3 protein, human; D053148:Caspase 3