Snake venom, bee venom and their components exert an anti-cancer effect by triggering apoptosis and cell cycle arrest in prostate cancer

R. Sayed, Mona Elrefay, AbirA. Elfiky, Hala F Zaki
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引用次数: 1

Abstract

Snake venom (SV), bee venom (BV) and their bioactive components are unique sources for cancer therapy development. The present study evaluated the anticancer potential of SV, BV and their major components (SV phospholipase A2 (svPLA2), melittin (MEL) and BV phospholipase A2 (bvPLA2)) against human prostate adenocarcinoma (PC3). Cytotoxicity was conducted using MTT biochemical assay. Genotoxicity was performed using real tine PCR for detection of pro-apoptotic and anti-apoptotic genes as well as the biomarker genes for prostate cancer. Cell arrest accumulation was highlighted using flowcytometry. MTT assay showed that treatment with SV and BV and their major components resulted in cellular morphological changes and significant cytotoxic effects in PC3. Furthermore, our results indicate that the svPLA2 gives much lower cytotoxic effect than the crude SV in PC3 cells in the highest tested concentration of 100 µg/ml. On the other hand, the major components of BV (bvPLA2 and MEL) showed more potent efficacy on PC3 cells than the crude BV. Interestingly, we showed that SV, svPLA2, BV, bvPLA2 and MEL suppressed the mRNA expression of the anti-apoptotic protein Bcl2, while increased the mRNA expression of the pro-apoptotic protein Bax. Moreover, they decreased the overexpressed prostate tumor marker genes. The cell cycle analysis showed that SV and svPLA2 arrested the cell cycle at G0/G1 phase, while BV, bvPLA2 and MEL arrested cell cycle at G2/M phase. In conclusion, our work demonstrated that SV, BV and their major components inhibit prostate cancer possibly via triggering apoptosis and cell cycle arrest.
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蛇毒、蜂毒及其成分在前列腺癌中通过触发细胞凋亡和细胞周期阻滞发挥抗癌作用
蛇毒(SV)、蜂毒(BV)及其生物活性成分是癌症治疗发展的独特来源。本研究评估了SV、BV及其主要成分(SV磷脂酶A2 (svPLA2)、melittin (MEL)和BV磷脂酶A2 (bvPLA2))对人前列腺腺癌(PC3)的抗癌潜力。MTT生化法测定细胞毒性。采用实时PCR检测促凋亡和抗凋亡基因以及前列腺癌的生物标志物基因进行遗传毒性检测。流式细胞术显示细胞阻滞积聚。MTT试验表明,SV和BV及其主要成分处理后,PC3细胞形态发生改变,细胞毒性显著。此外,我们的研究结果表明,在最高测试浓度为100 μ g/ml时,svPLA2对PC3细胞的细胞毒作用远低于粗SV。另一方面,BV的主要成分(bvPLA2和MEL)对PC3细胞的作用强于粗BV。有趣的是,我们发现SV、svPLA2、BV、bvPLA2和MEL抑制抗凋亡蛋白Bcl2的mRNA表达,而增加促凋亡蛋白Bax的mRNA表达。此外,它们还降低了前列腺肿瘤标记基因的过表达。细胞周期分析表明,SV、svPLA2阻滞细胞周期为G0/G1期,而BV、bvPLA2、MEL阻滞细胞周期为G2/M期。总之,我们的工作表明SV, BV及其主要成分可能通过触发细胞凋亡和细胞周期阻滞来抑制前列腺癌。
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