UroToday.com - Docetaxel (Doc) is the gold standard chemotherapy drug used clinically against androgen-independent prostate cancer (AI-PC) and when combined with prednisone results in a small but significant increase in survival. It is likely other drugs combined with Doc will further increase survival, which is the ultimate goal for treating patients with AI-PC. We chose to study the combination of 2-methoxyestradiol (2ME2) with Doc using preclinical models of human prostate cancer cell lines and the FG/Tag transgenic mouse model of AI-PC. Doc and 2ME2 target microtubules, block mitosis, and eventually increase apoptotic cell death. Although the combination of Doc + 2ME2 at first appears counterintuitive, i.e., they both have similar mechanisms targeting microtubules, our results provide interesting insights in preclinical models.

An attractive feature of 2ME2 is its non-toxic effect on normal cells and tissues. Since Doc has been shown to have neuropathy side effects in patients, our interest was to determine if lower, less toxic doses of Doc can be used in combination with 2ME2. Our results in prostate cancer cell lines and in the FG/Tag mice showed that lower doses of Doc combined with 2ME2 blocked mitosis and increased cell death via apoptosis or non-apoptotic mechanisms…