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

H. Shang, T. Wang, F. Shang, M. Li, Y. Luo, K.-M. Huang

Department of Gastroenterology, Zibo Central Hospital, Zibo, Shandong, China. eyanzi88@163.com

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• Pharmacology

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.

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