Anticancer Activity of Delphinium semibarbatum Alkaloid Fractions against LNCaP, and DU 145 Human Prostate Cancer Cells through the Intrinsic Apoptotic Pathway

Abstract

Prostate cancer is one of the common cancers with a high mortality rate in men. Therefore, there is always a necessity to discover new medications for treatment or alleviating its symptoms. In recent years, anticancer properties of a number of delphinium species were reported, but there is no study on the anticancer effects of Delphinium semibarbatum (D. semibarbatum) alkaloid contents. Therefore, this survey aimed to check the cytotoxicity and apoptotic properties of D. semibarbatum alkaloid fractions (DSAFs) against prostate cancer cells. Cytotoxicity was measured by MTT assay. We examined the apoptosis by detecting annexin V-FITC/PI staining, the mitochondrial membrane potential (Delta psi m) disruption, reactive oxygen species (ROS) generation, the activity of caspase-3, and expression of the Bax and Bcl-2 in cancer cells. DSAFs treatment inhibited the growth of LNCaP and DU-145 cells by the increase of apoptotic (Q2+Q3) cells detected by annexin V/PI assay. We found over-generation of intracellular ROS and Delta psi m loss in mitochondrial membrane potential treated cell lines. Attenuation of anti-apoptotic Bcl-2 followed by the increase in pro-apoptotic Bax bands, as well as activation of the caspase-3 enzyme was shown in Western blot analysis. Phytochemical analysis suggested that hetisine type diterpene alkaloids were probably responsible for apoptotic activities. Conclusively, the present study demonstrated that D. semibarbatum alkaloid content exerted antiproliferative effects against prostate cancer cells by inducing the intrinsic pathway of apoptosis.