title: Cinnamaldehyde affects the biological behavior of human colorectal cancer cells and induces apoptosis via inhibition of the PI3K/Akt signaling pathway.
abstract: Cinnamaldehyde (CA) is a bioactive compound isolated from the stem bark of Cinnamomum cassia, that has been identified as an antiproliferative substance with pro-apoptotic effects on various cancer cell lines in vitro. In the present study, the effects of CA on human colon cancer cells were investigated at both the molecular and cellular levels. Three types of colorectal cancer cells at various stages of differentiation and invasive ability (SW480, HCT116 and LoVo) were treated with CA at final concentrations of 20, 40 and 80 µg/ml for 24 h. Compared with the control group, the proliferation inhibition rate of the human colorectal cancer cells following treatment with CA increased in a dose- and time-dependent manner. The invasion and adhesion abilities of the cells were significantly inhibited as indicated by Transwell and cell-matrix adhesion assays. Meanwhile, CA also upregulated the expression of E-cadherin and downregulated the expression of matrix metalloproteinase-2 (MMP-2) and MMP-9. CA also elevated the apoptotic rate. The levels of pro-apoptotic genes were upregulated while the levels of apoptosis inhibitory genes were decreased which further confirmed the pro-apoptotic effect of CA. In order to explore the mechanism of CA-induced apoptosis, insulin-like growth factor-1 (IGF-1) and PI3K inhibitor (LY294002) were used to regulate the phosphoinositide 3-kinase (PI3K)/AKT pathway. The transcription activity of PI3K/AKT was markedly inhibited by CA, as well as IGF-1 which functions as an anti-apoptotic factor. In conclusion, CA has the potential to be developed as a new antitumor drug. The mechanisms of action involve the regulation of expression of genes involved in apoptosis, invasion and adhesion via inhibition of the PI3K/Akt signaling pathway.
authors.affiliation: Department of Oncology, The Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210029, P.R. China.
authors.forename: Jiepin
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Oncology, The Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210029, P.R. China.
authors.forename: Yuhao
authors.initials: Y
authors.lastname: Teng
authors.affiliation: Department of Oncology, The Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210029, P.R. China.
authors.forename: Shenlin
authors.initials: S
authors.lastname: Liu
authors.affiliation: Department of Commerce, The University of Melbourne, Victoria 3010, Australia.
authors.forename: Zifan
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Oncology, The Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210029, P.R. China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Oncology, The Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210029, P.R. China.
authors.forename: Yingying
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Oncology, The Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210029, P.R. China.
authors.forename: Songyang
authors.initials: S
authors.lastname: Xi
authors.affiliation: Department of Oncology, The Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210029, P.R. China.
authors.forename: Song
authors.initials: S
authors.lastname: Xu
authors.affiliation: Department of Oncology, The Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210029, P.R. China.
authors.forename: Ruiping
authors.initials: R
authors.lastname: Wang
authors.affiliation: Department of Oncology, The Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210029, P.R. China.
authors.forename: Xi
authors.initials: X
authors.lastname: Zou
mesh_terms: D000171:Acrolein / Q000008:administration & dosage / Q000031:analogs & derivatives*; D017209:Apoptosis / Q000187:drug effects; D015820:Cadherins / Q000096:biosynthesis / Q000235:genetics; D049109:Cell Proliferation / Q000187:drug effects; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D045325:HCT116 Cells; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000096:biosynthesis* / Q000235:genetics; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis / Q000235:genetics; D051058:Oncogene Protein v-akt / Q000096:biosynthesis* / Q000235:genetics; D019869:Phosphatidylinositol 3-Kinases / Q000096:biosynthesis* / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000171:Acrolein; D015820:Cadherins; D007334:Insulin-Like Growth Factor I; D020778:Matrix Metalloproteinase 2; D051058:Oncogene Protein v-akt; D019869:Phosphatidylinositol 3-Kinases; C012843:cinnamaldehyde