Pterostilbene as a Phytochemical Compound Induces Signaling Pathways Involved in the Apoptosis and Death of Mutant P53-Breast Cancer Cell Lines

Abstract

Pterostilbene is a natural nonflavonoid polyphenolic compound. It shows a remarkable range of biological activities, including antiproliferative, antiinflammatory, and antioxidant activity. However, the mechanism of action of PT in breast cancer cells containing mutant p53 protein has not been fully elucidated. Therefore, the present study was aimed at investigating the influence of PT on signaling pathways involved in the apoptosis of mutant p53-breast cancer cell lines. Immunocytochemistry and Western Immunoblotting techniques were used in this study. The present data showed that the viabilities and the proliferations of MDA-MB-231 and T-47D decreased significantly (P < 0.001) after treatment with different concentrations of PT. In addition, the morphological characteristics of both cell lines were changed after treatment with PT. Decreased protein expression of mutant p53 (R280 K, L194F) in MDA-MB-231 and T-47D breast cancer cell lines has also been achieved. In addition, overexpression of pro-apoptotic (Bax) protein, caspase-3 activity and histone release were increased after treatment of both cell lines with different PT concentrations. Furthermore, the protein expressions of cyclin D1, mTOR, and oncogenic β-catenin were significantly downregulated after treatment of both cell lines with PT. In conclusion, downregulations of protein expression of mutant p53, cyclin D1, mTOR, and β-catenin were increased after both cell lines had been treated with pterostilbene. PT could point to a promising use against the development and the progression of breast cancer as a natural therapeutic agent.