KMID : 0606920090170040403
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Biomolecules & Therapeutics 2009 Volume.17 No. 4 p.403 ~ p.411
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Anti-Cancer Effect of the Combination of Thiacremonone and Docetaxel by Inactivation of NF-kB in Human Cancer Cells
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Ban Jung-Ok
Lee Ung-Soo Noh Jin-Woo Moon Dong-Cheul Jeong Heon-Sang Lee Hee-Soon Hurh Byung-Serk Jung Jae-Kyung Han Sang-Bae Hong Jin-Tae Cho Jin-Suk Hwang In-Guk Kim Wun-Jae
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Abstract
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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-kB) is constitutively activated in the prostate cancer and activation of NF-kB 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-kB 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-kB. We found that the combination treatment of thiacremonone (50 mg/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-kB activity than those by the treatment of thiacremonone or docetaxel alone. It was also found that NF-kB 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-kB, and enhances the susceptibility of prostate cancer cells to docetaxel. Thus, thiacremonone could be useful as an adjuvant anti-cancer agent.
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KEYWORD
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Thiacremonone, Docetaxel, NF-kB, Apoptotic cell death, Prostate cancer
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