Pharmacogenomic determination of genes associated with sensitivity or resistance of tumor cells to curcumin and curcumin derivatives

Abstract

Curcuma longa L. has long been used as a medicinal plant in traditional Chinese medicine against abdominal disorders. Its active constituent curcumin has anti-inflammatory, chemopreventive and cytotoxic properties. In the present investigation, we have analyzed the cytotoxic activity of curcumin and four derivatives. Among these compounds, ethoxycurcumintrithiadiazolaminomethylcarbonate was the most cytotoxic one. The curcumin-type compounds were not cross-resistant to standard anticancer drugs and were not involved in ATP-binding cassette transporter-mediated multidrug resistance. A combined approach of messenger RNA-based microarray profiling, COMPARE analyses and signaling pathway analyses identified genes as determinants of sensitivity and resistance to curcumin and specific signaling routes involved in cellular response to curcumin. These genes may be useful as biomarkers to develop individualized treatment options in the future. From a nutritional point of view, it is a thriving perspective to further investigate whether C. longa may be used as a spice to improve cancer therapy.