The steroidogenic and morphological effects of paclitaxel on cultured ovarian cancer cells.
We have studied the biochemical effects of paclitaxel (trade name Taxol) in three ovarian cancer (OV Ca) cell lines and JEG-3 choriocarcinoma cells. Paclitaxel (1 microgram/ml) was cytotoxic to approximately 80% of OV Ca cells, and the ED50 ranged from 6 to 9 ng/ml. Paclitaxel was also cytotoxic to JEG-3 cells (ED50 40 ng/ml), but even at 1 microgram/ml, 40-50% of the cells survived paclitaxel treatment. Paclitaxel increased 17 beta-estradiol secretion 3-4 fold in all three OV Ca cell lines with an ED50 range of 3-13 ng/ml. Similarly, paclitaxel increased estradiol secretion from JEG cells with an ED50 of 50 ng/ml. Colchicine also increased estradiol secretion significantly from OV Ca cells at 2 microM while reducing cell number approximately 40% (beta-lumicolchicine, an inactive isomer, was ineffective at this concentration). Paclitaxel (1 microgram/ml) treatment of BR OV Ca cells produced alterations in morphology leading to "rounding" of cells within 6 h of treatment. Simultaneously, paclitaxel increased immunohistochemical staining for aromatase, and this increase was coincident with morphological alterations. The present results demonstrate that low concentrations of paclitaxel can have significant steroidogenic, as well as cytotoxic, effects on OV Ca cells, suggesting that paclitaxel may activate signal transduction pathways in addition to disrupting microtubule function. These findings further suggest that paclitaxel could be efficacious at submicromolar concentrations.
Cameron
M R
MR
Department of Obstetrics/Gynecology, University of Tennessee Medical Center, Knoxville 37920, USA.
Caudle
M R
MR
Sullivan
W R
WR
Peluso
J J
JJ
Wimalasena
J
J
D000230:Adenocarcinoma / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D000231:Adenocarcinoma, Papillary / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D000368:Aged; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D001141:Aromatase / Q000276:immunology / Q000378:metabolism; D003078:Colchicine / Q000494:pharmacology; D004958:Estradiol / Q000096:biosynthesis* / Q000378:metabolism / Q000494:pharmacology; D005260:Female; D006801:Humans; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D017239:Paclitaxel / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D000972:Antineoplastic Agents, Phytogenic; D004958:Estradiol; D001141:Aromatase; D017239:Paclitaxel; D003078:Colchicine