Histone deacetylase inhibitors enhance paclitaxel-induced cell death in ovarian cancer cell lines independent of p53 status.
BACKGROUND
Recurrence of drug-resistant disease contributes to the high mortality of ovarian cancer patients, which necessitates the identification of additional chemotherapeutic drugs. Histone deacetylase inhibitors (HDAIs) induce apoptosis in a number of malignant cell types and may represent a new class of drugs clinically relevant in the treatment of ovarian cancer.


METHODS
Ovarian cancer cells were treated with various combinations of a HDAI and paclitaxel (PTX). Cell death was measured using annexin V/propidium iodide exclusion.


RESULTS
The PTX/HDAI drug combination was as efficient in inducing cell death as continuous PTX treatment and superior to continuous HDAI treatment. Reversing the sequence of drug exposure reduced the cytotoxic efficacy of the drug combination. The p53 status of the cell lines did not alter the cytotoxic efficacy of the treatment protocols.


CONCLUSIONS
These results suggest that HDAIs possess possible clinical applications as an adjuvant therapy in the treatment of ovarian cancer.
Chobanian
Nishan H
NH
Division of Gynecologic Oncology, University of Kentucky, 800 Rose Street, Lexington, Kentucky 40536, USA.
Greenberg
Victoria L
VL
Gass
Jennifer M
JM
Desimone
Christopher P
CP
Van Nagell
John R
JR
Zimmer
Stephen G
SG
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002087:Butyrates / Q000008:administration & dosage / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D004357:Drug Synergism; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D056572:Histone Deacetylase Inhibitors; D006801:Humans; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D017239:Paclitaxel / Q000008:administration & dosage / Q000494:pharmacology*; D016159:Tumor Suppressor Protein p53 / Q000037:antagonists & inhibitors / Q000096:biosynthesis*
D002087:Butyrates; D004791:Enzyme Inhibitors; D056572:Histone Deacetylase Inhibitors; D016159:Tumor Suppressor Protein p53; D017239:Paclitaxel