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. MATERIALS AND 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. CONCLUSION: 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.
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. MATERIALS AND 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. CONCLUSION: 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.
Authors: Hemant K Roy; Bola F Olusola; Dahn L Clemens; William J Karolski; Anne Ratashak; Henry T Lynch; Thomas C Smyrk Journal: Carcinogenesis Date: 2002-01 Impact factor: 4.944
Authors: Christopher S Beevers; Long Chen; Lei Liu; Yan Luo; Nicholas J G Webster; Shile Huang Journal: Cancer Res Date: 2009-01-27 Impact factor: 12.701
Authors: L Andy Chen; Jing Li; Scott R Silva; Lindsey N Jackson; Yuning Zhou; Hiroaki Watanabe; Kirk L Ives; Mark R Hellmich; B Mark Evers Journal: J Biol Chem Date: 2008-11-21 Impact factor: 5.157
Authors: Mark A Feitelson; Alla Arzumanyan; Rob J Kulathinal; Stacy W Blain; Randall F Holcombe; Jamal Mahajna; Maria Marino; Maria L Martinez-Chantar; Roman Nawroth; Isidro Sanchez-Garcia; Dipali Sharma; Neeraj K Saxena; Neetu Singh; Panagiotis J Vlachostergios; Shanchun Guo; Kanya Honoki; Hiromasa Fujii; Alexandros G Georgakilas; Alan Bilsland; Amedeo Amedei; Elena Niccolai; Amr Amin; S Salman Ashraf; Chandra S Boosani; Gunjan Guha; Maria Rosa Ciriolo; Katia Aquilano; Sophie Chen; Sulma I Mohammed; Asfar S Azmi; Dipita Bhakta; Dorota Halicka; W Nicol Keith; Somaira Nowsheen Journal: Semin Cancer Biol Date: 2015-04-17 Impact factor: 15.707