Abstract

Background: Curcumin, a polyphenol from turmeric, has potent anticancer properties in human cancer cell lines. Nevertheless, its multitargeting clinical application in cancer and other diseases is hampered by its poor systemic bioavailability. A novel curcumin derivative "NCD" was developed through covalent modification of the curcumin "CUR" molecule on sites remote from its natural functional groups.

Methods: The NCD was tested for its anticancer effect against six human cancer cell lines in comparison to CUR and the standard anticancer drug Doxorubicin "DOX". In vivo structure-action relationship to the dose-dependent inducible plasma Glutathione S-transferase (GST) was studied. Plasma GST activity was estimated one and half and 24 hours after oral administration of each of CUR and the NCD.

Results: The NCD showed significantly lower Half-maximal inhibitory concentrations (IC50s) as compared to the DOX with each of HELA, the human cervical, MCF7, the human breast and HCT116, the human colonic cancer cell lines. Significant improvements in terms of lower IC50 as compared to CUR with all tested human cancer cell lines were also found. In vivo, the NCD showed significant elevations in inducible plasma GST in the 1.5 hr and the 24 hr duration studies as compared to CUR.

Conclusion: The IC50 anticancer effect of the NCD significantly was improved against six human cancer cell lines in comparison to CUR. The NCD retained an improved potency in terms of in vivo structure-action relationship to dose-dependent induction of plasma GST. With GST as biomarker for cancer, it should not be taken as parameter in studies and/or clinical trial involving both cancer and CUR as GST is dosedependently inducible by CUR and some of its derivatives.