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

作者:Ban Jung Ok; Cho Jin Suk; Hwang In Guk; Noh Jin Woo; Kim Wun Jae; Lee Ung Soo; Moon Dong Cheul; Jeong Heon Sang; Lee Hee Soon; Hwang Bang Yeon; Jung Jae Kyung; Han Sang Bae; Hong Jin Tae*
来源:Biomolecules & Therapeutics, 2009, 17(4): 403-411.
DOI:10.4062/biomolther.2009.17.4.403

摘要

Thiacremonone, the main component isolated from heated garlic (Allium sativum L.), is interested 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-kappa B) is constitutively activated in the prostate cancer and activation of NF-kappa B is implicated in drug resistance in cancer cells. Docetaxel, a semisynthetic analog of paclitaxel, is an antineoplastic drug widely used for advanced various cancer. In previous studies, we found that thiacremonone inhibited activation of NF-kappa B in cancer cells and marcrophages. In the present study, we investigated whether thiacremonone could increase susceptibility of prostate cancer cells (PC-3 and DU145) to docetaxel via inactivation of NF-kappa B. We found that the combination treatment of thiacremonone (50 mu g/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-kappa B activity than those by the treatment of thiacremonone or docetaxel alone. It was also found that NF-kappa B target gene expression of Bax, caspase-3 and caspase-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-kappa B, and enhances the susceptibility of prostate cancer cells to clocetaxel. Thus, thiacremonone could be useful as an adjuvant anti-cancer agent.

  • 出版日期2009-10-31