We aimed to investigate the apoptotic effects of the methanolic extract of Dorema glabrum seed on WEHI-164, cancerous cells in comparison with L929, normal cells and compared them with the cytotoxic effects of Taxol. So, MTT test and DNA fragmentation assay were performed on cultured and treated cells. Also electrophoresis which was followed by immunoblotting was done to survey the production of Caspase-3 and Bcl2 proteins, and to inquire into their relative genes expression, RT-PCR was used. According to our findings, the methanolic extract of Dorema glabrum seed can alter cells morphology as they shrink and take a spherical shape and lose their attachment too. So, the plant extract inhibits cell growth albeit in a time- and dose-dependent manner and results in degradation of chromosomal DNA. Induction of apoptosis by the plant extract was proved by the reduction of pro-Caspase-3 and Bcl2 proteins and increase in Caspase-3 gene expression and decrease in that of bcl2 too. Our data well established the antiproliferative effect of methanolic extract of Dorema glabrum seed and clearly showed that the plant extract can induce apoptosis and not necrosis in vitro. These results demonstrated that Dorema glabrum seed might be a novel and attractive therapeutic candidate for tumor treatment. 1. Introduction Normal cells grow and divide in an ordered fashion, in accordance with the cell cycle. Defective apoptosis (programmed cell death) which results in enhanced growth describes most cancer cells [1]. Several proteins control the timing of the events in the cell cycle, which is tightly regulated to ensure that cells divide only when necessary. The loss of this regulation is the hallmark of cancer [1, 2]. Initially, somatic cell fusion and nuclear transplantation studies, together with the selective use of growth factors and inhibitors of macromolecular biosynthesis, established the fundamental parameters of cell cycle regulation [3, 4]. Our understanding of the complexities of apoptosis and the mechanisms evolved by tumor cells to resist engagement of cell death has focused research effort into the development of strategies designed to selectively induce apoptosis in cancer cells [5–7]. Several previous studies demonstrated that certain phytochemicals present in medicinal herbs exert antitumorigenic activity by inducing apoptosis in cancer cells [8–11]. The mechanism, of apoptosis are now mostly well known, involving activation of caspases (cysteinyl, aspartate-specific proteases), which cleave to inactivate or activate target substrates within a cell [5] and
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