Curcumin Sensitizes 4T1 Murine Breast Cancer Cells to Cisplatin Through PAR4 Secretion

Background/Aim: Prostate apoptosis response 4 (PAR4), a tumour-suppressor protein, selectively induces apoptosis of cancer cells without affecting normal cells. Its soluble form is induced by secretagogues (e.g., chloroquine), and it induces apoptosis by interacting with the receptor of glucose-regulated protein 78, which is overexpressed in cancer cells. In this study, curcumin was analyzed as an inducer of PAR4 expression in 4T1 murine breast cancer cell. and its ability to induce PAR4 secretion in Balb/c mice. In addition, the cisplatin sensitizing effect of soluble PAR4 was analyzed. Material and Methods: The 4T1 cell line was treated in vitro using different concentrations of curcumin; cell viability was analyzed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and PAR4 expression by western blotting. The expression of soluble PAR4 in the serum of mice treated with intraperitoneal curcumin was analyzed using the dot-blot method. Moreover, MTT assay was used to analyze the effects of serum from curcumin-treated mice on cell viability. Tumor size was analyzed in mice treated with curcumin alone and in combination with cisplatin. Results: Curcumin showed a dose- and time-dependent effects on cell viability on 4T1 cells, as well as increasing PAR4 expression. Compared with the control group (phosphate-buffered saline), mice treated with curcumin showed an increase in plasma PAR4. In the Balb/C tumor model, mice treated with curcumin and cisplatin showed greater tumor shrinkage than the control group. Conclusion: These results indicate that curcumin induces expression of soluble PAR4 and sensitizes tumor cells to cisplatin.