Curcumin inhibits proliferation of colorectal carcinoma by modulating Akt/mTOR signaling.

Curcumin, a natural polyphenol product of the plant Curcuma longa, has been shown to inhibit the growth and progression of colorectal cancer; however, the anticancer mechanism of curcumin remains to be elucidated.Colorectal cancer cells were treated with curcumin and changes in proliferation, protein and mRNA levels were analyzed.Curcumin inhibited proliferation of colorectal cancer cells. This effect was mediated by inhibition of mammalian target of rapamycin (mTOR) signaling as evidenced by decreased phosphorylation of downstream effectors of mTOR complex 1 (mTORC1), p70S6K and 4E-BP1. Curcumin decreased total expression of mTOR, Raptor and Rictor protein and mRNA levels. Surprisingly, curcumin induced phosphorylation of Akt(Ser 473); this effect may be attributed to a decrease in levels of the PHLPP1 phosphatase, an inhibitor of Akt.Our data suggest that curcumin, a natural compound, may exert its antiproliferative effects by inhibition of mTOR signaling and thus may represent a novel class of mTOR inhibitor.