Potent inhibition of tubulin polymerisation and proliferation of paclitaxel-resistant 1A9PTX22 human ovarian cancer cells by albendazole.
BACKGROUND
Resistance to paclitaxel (PTX) is a major concern in treating ovarian cancer. Thus, agents effective in taxane-resistant tumours are highly sought. It has recently been shown that albendazole (ABZ) is a potent inhibitor of cell proliferation, angiogenesis and tumour growth. This study was designed to examine the efficacy of ABZ in PTX-resistant human ovarian cancer 1A9PTX22 cells.


METHODS
Using both the parent PTX-sensitive 1A9 and PTX-resistant sub-line 1A9PTX22 cells, the effects of both drugs on cell proliferation, tubulin polymerisation and microtubule distribution across the cell was investigated.


RESULTS
Comparison of the inhibitory concentration to achieve 50% cell death (IC(50)) revealed that, unlike PTX, ABZ is highly efficacious in inhibiting proliferation of 1A9PTX22 cells. The finding that ABZ but not PTX is highly effective in disrupting tubulin polymerisation in these cells confirmed involvement of the tubulin pathway.


CONCLUSIONS
Data from this study suggest that ABZ is effective in suppressing growth of PTX-resistant ovarian tumour cells.
Cancer Research Laboratories, University of New South Wales Department of Surgery, St. George Hospital (SESIAHS), Sydney, NSW 2217, Australia.
Stephanie W L
SW
Chu
Samina
S
Badar
David L
DL
Morris
Mohammad H
MH
Pourgholami
D015766:Albendazole / Q000494:pharmacology*; D048708:Cell Growth Processes / Q000187:drug effects; D019008:Drug Resistance, Neoplasm; D004354:Drug Screening Assays, Antitumor; D005260:Female; D006801:Humans; D008870:Microtubules / Q000187:drug effects / Q000378:metabolism; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D017239:Paclitaxel / Q000494:pharmacology*; D014404:Tubulin / Q000378:metabolism*; D050257:Tubulin Modulators / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D014404:Tubulin; D050257:Tubulin Modulators; D015766:Albendazole; D017239:Paclitaxel