Over-expression of DJ-1 attenuates effects of curcumin on colorectal cancer cell proliferation and apoptosis

Objective: The Phosphatase and tensin homologue deleted on chromosome ten (PTEN) acts as a tumor suppressor gene by inhibiting the phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) signaling pathway. DJ-1, a negative regulator of PTEN, is associated with the pathogenesis of a variety of tumors. Curcumin (Cur) is a phenolic compound that is extracted from various plant rhizomes with various anti-tumor pharmacological effects. This study aimed to investigate the effects of Cur on proliferation and Apoptosis of colorectal Cancer cells.

Materials and methods: Human normal colorectal epithelial cell line (NCM460) and colorectal Cancer cell line (SW480 and SW620) were cultured in vitro. Real-time quantitative PCR (RT-PCR) and western blot were used to detect DJ-1 and PTEN mRNA and protein, respectively. Cell Apoptosis was determined with flow cytometry. SW480 cells were divided into control, 20 μM Cur treatment group, Cur+pcDNA3.1-Blank group and Cur+pcDNA3.1-DJ-1 group. Cell proliferation activity was evaluated with EdU staining.

Results: Comparing with NCM460 cells, DJ-1 was significantly increased, while PTEN was significantly declined in SW480 and SW620 cells (p<0.05). Cur treatment significantly inhibited SW480 and SW620 cell proliferation and significantly induced Apoptosis compared to control group (p<0.05) but showed no significant effects on NCM460 cells. Cur down-regulated DJ-1 level and enhanced PTEN expressions in SW480 cells with dose dependence. The pcDNA3.1-DJ-1 transfection significantly declined PTEN expression, enhanced p-AKT levels, reduced cell Apoptosis, and strengthened cell proliferation in SW480 cells treated by Cur (p<0.05).

Conclusions: Cur can inhibit colorectal Cancer cell proliferation and promote Apoptosis by down-regulating DJ-1 expression to regulate the activity of PTEN/PI3K/Akt signaling pathway.