Apoptotic effects of Tian-Long compound on endometrial adenocarcinoma cells in vitro.
The Tian-Long (TL) compound is a water-soluble extract of six Chinese medicinal herbs. To explore its antitumor properties and the mechanism for activity in gynecological malignancies, the present studies were carried out using Ishikawa cells derived from uterine endometrial adenocarcinoma. Morphologically, cell death and decrease in the number of viable cells were observed in the presence of the TL compound. The proliferation of Ishikawa cells was significantly suppressed in a time- and dose-dependent manner, as indicated by both the WST-1 and the BrdU incorporation assay. Results from both the WST-1 and the BrdU incorporation assay demonstrated that the compound could inhibit the cell proliferation despite the presence of 17beta-estradiol in the medium. It is generally noted that the disturbance in mitochondrial function and DNA synthesis during cell proliferation can result in apoptosis. Being consistent with this notion, redistribution of the plasma membrane phosphatidylserine was identified with fluoromicroscopy and flow cytometry. Analysis of the fluorescent patterns of JC-1 staining revealed depolarization of the mitochondrial membrane in the exposed cells. Moreover, the amount of Bcl-2 enhanced in the presence of 17beta-estradiol was repressed by the compound. The present results indicate that the ingredients of TL compound are very promising for use in the treatment of endometrial adenocarcinoma. Further studies are necessary to elucidate the therapeutic mechanisms in its antitumor activity.
Li
Zhong-Lian
ZL
Department of Anatomy and Cell Biology, Osaka Medical College, 2-7 Daigaku-machi, Takatsuki, Osaka, 569-8686, Japan.
Morishima
Syoko
S
Tang
Jin-Tian
JT
Otsuki
Yoshinori
Y
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004273:DNA, Neoplasm / Q000096:biosynthesis; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D016889:Endometrial Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D004958:Estradiol / Q000494:pharmacology; D005260:Female; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D010718:Phosphatidylserines / Q000378:metabolism; D008517:Phytotherapy; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism
D000972:Antineoplastic Agents, Phytogenic; D004273:DNA, Neoplasm; D004365:Drugs, Chinese Herbal; D010718:Phosphatidylserines; D019253:Proto-Oncogene Proteins c-bcl-2; D004958:Estradiol; C505407:CASP3 protein, human; C506433:CASP9 protein, human; D053148:Caspase 3; D053453:Caspase 9