Palmatine modulates triple negative mammary carcinoma by regulating the endogenous function of p53, p21 and Mdm2

Abstract

Natural products and their bioactive constituents have been investigated for centuries and recognized as a source of valuable therapeutic candidates in the development of contemporary anticancer drugs. Triple negative breast cancers are a subtype of malignant cells formed in the breast tissue caused by uncontrolled and abnormal division. Palmatine, a naturally occurring alkaloid extracted from several medicinal plants in West Africa, has not been extensively investigated for its anti-breast cancer properties especially in triple-negative mammary carcinoma. The 4T1 triple-negative breast cancer cells were transplanted orthotopically into the mammary fat pad of the female balb/c mice. Tumor volume, tumor weight, histology and immunohistochemical analysis were carried out. After 28 days, palmatine (1, 5 and 10 mg/kg) in a dose-dependent manner decreased tumor volume (190.80 ± 19.14, 25.40 ± 2.82, 14.20 ± 1.85), reduced tumor weight (1.035 ± 0.04, 0.8027 ± 0.01, 0.5090 ± 0.04), inhibited tumor growth (31%, 46%, 66%) and protected against morphological dysplasia induced by the carcinoma (3.50 ± 0.29, 2.25 ± 0.25, 1.75 ± 0.25) respectively. Also, palmatine increased the activity of the tumor protein p53, cyclin-dependent kinase inhibitor 1 (p21) and mouse double minute 2 (Mdm2) compared to the untreated carcinoma bearing mice. Overall, palmatine protected against triple negative mammary carcinoma and can be a valuable anticancer compound to treat breast diseases.