Targeting the mercapturic acid pathway and vicenin-2 for prevention of prostate cancer.

ABSTRACT

Prostate cancer (CaP) is often androgen-sensitive malignancy and regresses upon inhibition of androgen signaling. However, CaP, nearly always develops androgen resistance and progresses to aggressive and lethal androgen-independent CaP, which lacks satisfactory therapy. For metastatic CaP, patients are often treated with Taxotere (docetaxel), a cytoskeleton-targeted chemotherapy drug, that provides transient palliative benefit but to which patients rapidly develop drug-resistance. Combination chemotherapy may be used instead, but is more toxic and adds little clinically relevant benefit over docetaxel. Therefore, novel strategies to enhance docetaxel efficacy are needed to effectively treat patients with metastatic CaP. The mercapturic acid pathway, which metabolizes genotoxic and pro-apoptotic toxins, is over-expressed in CaP and plays an important role in carcinogenesis, metastasis and therapy-resistance of CaP. Vicenin-2, a flavonoid derived from Tulsi (holy basil) as an active compound, inhibits the growth of CaP and increases the anti-tumor activity of docetaxel in-vitro and in-vivo. Taken together, the combination of vicenin-2 and docetaxel could be highly effective in the treatment of advanced and metastatic CaP due to their multi-targeting anti-tumor potential.