Transient metals enhance cytotoxicity of curcumin: potential involvement of the NF-kappaB and mTOR signaling pathways.

BACKGROUND/AIM Curcumin has been recognized as a metal-binding compound and an anticancer agent, yet the involvement of metals in the anticancer action of curcumin remains unclear. The present study examined the role of transient metals in curcumin-induced cytotoxicity in cancer cells. MATERIALS AND METHODS Metal-binding activity and cytotoxicity of curcumin were examined in human cancer lines with cell viability assay, confocal microscopy, Western blot, and measurement of hydrogen peroxide generation. RESULTS It was found that Cu (II) most significantly potentiated the cytotoxicity of curcumin among the metals tested. The combination of curcumin and Cu (II) did not generate reactive oxygen species and vitamin E did not block the cytotoxicity. Curcumin plus Cu (II) enhanced intracellular copper levels and potentiated curcumin-induced suppression of the nuclear factor kappa B (NF-κB) pathway, as well as alterations of mammalian target of rapamycin-raptor (mTOR) signaling. CONCLUSION Transient metals enhance the cytotoxicity of curcumin, likely through targeting of the NF-κB and mTOR signaling pathways.