Abstract
Objective:
To improve the poor efficacy (< 10%) of chemotherapy for patients with hormone-refractory prostate cancer, we investigated a possible cytotoxic effect of carmustine/β-glucan combination on prostatic cancer PC-3 cells, focusing on a glutathione-dependent detoxifying enzyme, glyoxalase I (Gly-I).
Methods:
Carmustine (BCNU) is an anticancer agent and a putative inhibitor of Gly-I, while β-glucan is a unique, nontoxic polysaccharide extracted from maitake mushrooms. The cytotoxic effects of BCNU or other anticancer agents with β-glucan on PC-3 cells were assessed by cell-viability testing and Gly-I activity was measured using the spectrophotometric method.
Results:
BCNU, 5-fluorouracil (5-FU), and methotrexate (MTX) were capable of inducing approximately a 50% reduction in cell viability at 72 hours, while etoposide, cisplatin, and mitomycin C were all ineffective. Only the combination of BCNU (50 μmol) and β-glucan (60 μg/mL) exhibited an enhanced cytotoxicity with an approximate 90% cell viability reduction, but little improvement was seen with any combinations of 5-FU, MTX, or β-glucon. Gly-I assays revealed that such a profound (∼90%) cell death was accompanied by an approximate 80% reduction in Gly-I activity by 6 hours.
Conclusion:
This study demonstrates a sensitized cytotoxic effect of BCNU with β-glucan in PC-3 cells, which was associated with a drastic (∼80%) inactivation of Gly-I. Therefore, the BCNU/β-glucan combination may help to improve current treatment efficacy by targeting Gly-I, which appears to be critically involved in prostate cancer viability.
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