Studies on the Cytotoxic Activities of Punica granatum L. var. spinosa (Apple Punice) Extract on Prostate Cell Line by Induction of Apoptosis

The Punica granatum L. var. granatum (pomegranate) has been demonstrated to exert antitumor effects on various types of cancer cells. The present study aimed to evaluate the medicinal herbs Punica granatum L. var. spinosa (apple punice) that are native to Iran. This study was determined to test the possible cytotoxic activity and induction of apoptosis on human prostate cell lines. The effect of ethanol extracts of the herbs on the inhibition of cell proliferation was assessed by MTT colorimetric assay. PC3 cell lines treated with the extracts were analyzed for the induction of apoptosis by cell death detection (ELISA) and TUNEL assay. Dye exclusion analysis was performed for viability rate. Our results demonstrated that the Punica granatum L. var. spinosa extract dose dependently suppressed the proliferation of PC3 cells (IC50= 250.21？μg/mL) when compared with a chemotherapeutic anticancer drug (Toxol) (Vesper Pharmaceuticals) with increased nucleosome production from apoptotic cells. The Punica granatum L. var. spinosa extract attenuated the human prostate cell proliferation in vitro possibly by inducing apoptosis. The Punica granatum L. var. spinosa is likely to be valuable for the treatment of some forms of human prostate cell line. 1. Introduction Apoptosis (programmed cell death) is a physiological mechanism of cell death. During apoptosis, there is a rapid reduction in the cellular volume followed by chromatin condensation, associated with characteristic internucleosomal DNA cleavage. This results in the production of nucleosomes of DNA fragments complexes with core histones, which are distinct multiples of an 180–200？bp subunit [1]. Cancer is one of the major causes of mortality throughout the world. World Health Organization statistics have estimated that cancer will cause 83.2 million deaths between 2005 and 2015 if the recommended measures are not respected. In 2007, cancer was the cause of 7.9 million deaths, which is 13% of world mortality. Among males in the third world countries, prostate cancer is the second-leading cause of cancer-related death [2]. Cancer is a disease that is characterized by too little apoptosis. Under normal circumstances damaged cells will undergo apoptosis, but in the case of cancer cells mutations may have occurred that prevent cells from undergoing apoptosis. Understanding apoptosis regulation is a main concern in the development of chemotherapeutic anticancer drugs on malignant cells [3, 4]. Traditionally, many extracts from roots, stems, and fruits have been used for maintaining health, enhancing overall immune