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Chemotherapy-induced apoptosis in epithelial ovarian cancers
L J Havrilesky1, A Elbendary, J A Hurteau
1Department of Obstetrics and Gynecology, Duke University Medical Center, Durham, North Carolina, USA.
Objective:
To determine whether chemotherapy drugs elicit programmed cell death (apoptosis) in ovarian cancer cells.
Methods:
Monolayers of immortalized ovarian cancer cell lines and primary ovarian cancer cells obtained from ascites were grown in the presence of cisplatin, 4-hydroxyperoxy-cyclophosphamide (the active metabolite of cyclophosphamide) or paclitaxel. Next, DNA was extracted from the cells and subjected to electrophoresis to determine if DNA laddering characteristic of apoptosis was present.
Results:
In three of six immortalized cell lines (OVCA 420, 429, and 433), apoptosis was not seen in response to any of the three drugs. In contrast, in OVCAR-3 and OVCA 432, DNA laddering consistent with apoptosis was observed in response to all three drugs. In the DOV 13 cell line, apoptosis was seen only with 4-hydroxyperoxycyclophosphamide. Among three primary ovarian cancers, cisplatin elicited apoptosis in one case. Both cell lines with mutant p53 genes (OVCAR-3 and OVCA 432) underwent apoptosis in response to all three drugs, whereas among three cell lines known to have normal p53 genes, one underwent apoptosis in response to 4-hydroxyperoxycyclophosphamide and two were unaffected.
Conclusion:
Ovarian cancer cell death in response to commonly used chemotherapeutic drugs involves the induction of a genetically programmed sequence of events (apoptosis) rather than simply necrosis.