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

Document Type : Research article

Authors

1 Department of Pharmacognosy, School of Pharmacy, Shahid Beheshti University of Medical Science, Tehran, Iran.

2 Department of Pharmacognosy, School of Pharmacy, Shaheed Sadoughi University of Medical Science and Health Service, Yazd, Iran.

3 Department of Pharmacognosy, Isfahan Pharmaceutical Sciences Research Center, School of Pharmacy, Isfahan University of Medical Sciences, Isfahan, Iran.

4 Phytochemistry Research Center, Shahid Beheshti University of Medical Science, Tehran, Iran.

5 Department of Clinical Biochemistry, School of Pharmacy, Isfahan University of Medical Sciences, Isfahan, Iran.

6 Department of Medical Chemistry, Phytochemistry Research Center, School of Pharmacy, Shahid Beheshti University of Medical Science, Tehran, Iran.

10.22037/ijpr.2021.115462.15382

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 (ΔΨm) 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 ΔΨm 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.

Graphical Abstract

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

Keywords


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