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


METHODS
Colorectal cancer cells were treated with curcumin and changes in proliferation, protein and mRNA levels were analyzed.


RESULTS
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.


CONCLUSIONS
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.
Johnson
Sara M
SM
Department of Surgery, The University of Texas Medical Branch, Galveston, TX 77550, USA.
Gulhati
Pat
P
Arrieta
Isela
I
Wang
Xiaofu
X
Uchida
Tatsuo
T
Gao
Tianyan
T
Evers
B Mark
BM
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism; D000970:Antineoplastic Agents / Q000494:pharmacology*; D015153:Blotting, Western; D018797:Cell Cycle Proteins; D049109:Cell Proliferation / Q000187:drug effects*; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D003474:Curcumin / Q000494:pharmacology*; D006801:Humans; D000076222:Mechanistic Target of Rapamycin Complex 1; D046912:Multiprotein Complexes; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation; D011506:Proteins; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000235:genetics / Q000378:metabolism; D058570:TOR Serine-Threonine Kinases; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D048868:Adaptor Proteins, Signal Transducing; D000970:Antineoplastic Agents; D018797:Cell Cycle Proteins; C087000:EIF4EBP1 protein, human; D046912:Multiprotein Complexes; D010750:Phosphoproteins; D011506:Proteins; D012333:RNA, Messenger; D014157:Transcription Factors; D000076222:Mechanistic Target of Rapamycin Complex 1; D051057:Proto-Oncogene Proteins c-akt; D038762:Ribosomal Protein S6 Kinases, 70-kDa; D058570:TOR Serine-Threonine Kinases; D003474:Curcumin