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.