Modulation of the interplay between p53, ICAM-1 and VEGF in drug-treated LoVo colon cancer cells

Camelia Hotnog, Mirela Mihaila, Liliana Puiu, Anca Botezatu, Viviana Roman, Marinela Bostan, Lorelei Brasoveanu
Romanian Biotechnological Letters   unpublished
Uncontrolled cellular proliferation characterizes the tumor growth and metastasis, usually being the result of multiple genetic and epigenetic insults to the cell, particularly involving proto-oncogenes and tumor suppressor genes. The angiogenesis process, inducted by a tumor, is a controlled process, influenced by angiogenic and angiostatic factors, that involves a complex interaction between tumor and endothelial cells. Tumor cell invasion and metastasis are promoted by the upregulation of
more » ... upregulation of angiogenic factors, such as vascular endothelial growth factor (VEGF), or of cell adhesion molecules, like intercellular adhesion molecule (ICAM-1). Angiogenesis may partially be regulated by the function of TP53, in terms of downregulation of angiogenic factor expression, whereas dysfunctional p53 stimulates angiogenesis by upregulating VEGF. Moreover, genotoxic activation of p53 leads to up-regulation of intracellular-adhesion molecule-1 (ICAM-1) mRNA and protein. Contrast data are available on the anti-cancer effects of nutraceuticals, like resveratrol (Rsv) and curcumin (Crm) in colon cancer, for their potential clinical application when used in combination with anti-cancer drugs. Therefore, the aim of the present study focused on the investigation of the regulatory roles of resveratrol and curcumin on cell proliferation, apoptosis, and gene expression of selected apoptosis, angiogenesis or cellular adhesion-related proteins in LoVo colon cancer cell line. The interplay between genes coding molecules associated to apoptosis, angiogenesis and adhesion were differentially modulated by single and combined treatments, and additive effects of Rsv and Crm to 5-FU treatments were observed.