Data from Thiacremonone Augments Chemotherapeutic Agent–Induced Growth Inhibition in Human Colon Cancer Cells through Inactivation of Nuclear Factor-κB

Abstract

<div>Abstract<p>Chemotherapeutic strategies commonly use multiple agents to overcome drug resistance and to lower drug toxicity. Activation of nuclear factor-κB (NF-κB) is implicated in drug resistance in cancer cells. Previously, we reported that thiacremonone, a novel sulfur compound isolated from garlic, inhibited NF-κB and cancer cell growth with IC<sub>50</sub> values about 100 μg/mL in colon cancer cells. In the present study, we tested whether thiacremonone could increase susceptibility of cancer cells to chemotherapeutics through inactivation of NF-κB. Colon cancer cells were cotreated with thiacremonone (50 μg/mL, half dose of IC<sub>50</sub>) and lower doses of each chemotherapeutic agent (half dose of IC<sub>50</sub>) for 24 hours. NF-κB activity was completely abrogated in cells treated with a combination of thiacremonone and docetaxel, whereas thiacremonone on its own did not alter NF-κB activity. This combined drug effect was also found with other anticancer drugs in colon cancer and in other cancer cells. In good correlation with inhibition of cell growth and NF-κB activity, the combination treatment also regulated NF-κB target genes. Oral treatment of mice with thiacremonone (1 mg/kg) by administering it in drinking water for 4 weeks significantly augmented docetaxel (1 mg/kg, i.p., four times)–induced decrease of tumor growth accompanied with regulation of NF-κB activity and NF-κB target genes. These results warrant carefully designed clinical studies investigating the combination of thiacremonone and commonly used chemotherapeutic agents for the treatment of human cancers. (Mol Cancer Res 2009;7(6):870–9)</p></div>