Anti-Cancer Effect of the Combination of Thiacremonone and Docetaxel by Inactivation of NF-κB in Human Cancer Cells

Abstract

Abstract － Thiacremonone, the main component isolated from heated garlic ( Allium sativum L.), is inter-ested for using as a cancer preventive or therapeutic agent since garlic has been known to be useful plant in the treatment of cancers. Nuclear factor kappaB (NF-κB) is constitutively activated in the prostate cancer and activation of NF-κB is implicated in drug resistance in cancer cells. Docetaxel, a semisynthetic analog of pa-clitaxel, is an antineoplastic drug widely used for advanced various cancer. In previous studies, we found that thiacremonone inhibited activation of NF-κB in cancer cells and marcrophages. In the present study, we in-vestigated whether thiacremonone could increase susceptibility of prostate cancer cells (PC-3 and DU145) to docetaxel via inactivation of NF-κB. We found that the combination treatment of thiacremonone (50 μg/ml) with docetaxel (5 nM) was more effective in the inhibition of prostate cancer cell growth and induction of apoptosis accompanied with the significant inhibition of NF-κB activity than those by the treatment of thiacre-monone or docetaxel alone. It was also found that NF-κB target gene expression of Bax, caspase-3 and cas-pase-9 was much more significantly enhanced, but the expression of Bcl-2 was also much more significantly inhibited by the combination treatment. These results indicate that thiacremonone inhibits NF-κB, and enhan-ces the susceptibility of prostate cancer cells to docetaxel. Thus, thiacremonone could be useful as an ad-juvant anti-cancer agent.Keywords: Thiacremonone, Docetaxel, NF-κB, Apoptotic cell death, Prostate cancer