Rozman Antolikova Natalia, Kello Martin, Zigova Martina, Tischlerova Viera, Petrilla Vladimir, Pirnik Zdeno, Mojzisova Gabriela, Mojzis Jan
Department of Pharmacology and Toxicology, University of Veterinary Medicine and Pharmacy, Kosice, Slovakia.
Department of Pharmacology, Faculty of Medicine, P.J. Safarik University, Tr. SNP 1, Kosice, Slovakia.
Acta Biochim Pol. 2019 Jun 7;66(2):207-213. doi: 10.18388/abp.2018_2779.
In the present study, we investigated the antiproliferative activity of Naja ashei full venom (NAV) on human colorectal cancer cells. The NAV-induced antiproliferative effect was associated with cell cycle arrest in S phase and increased number of cells with sub G0/G1 DNA content, which is considered a marker of apoptosis. Apoptosis has also been confirmed with annexin V/PI staining. Furthermore, flow cytometric analysis revealed loss of mitochondrial membrane potential with concomitant increase in cytochrome c and Smac/DIABLO protein content. These effects were associated with the activation of caspase-9 and caspase-3, as well as with PARP cleavage. Moreover, phosphorylation of antiapoptotic Bcl-2 protein in NAV-treated HCT116 was observed. In conclusion, our study for the first time documented antiproliferative/pro-apoptotic effect of NAV in colorectal cancer cells. Our results strongly suggest the involvement of mitochondria in NAV induced apoptosis of cancer cells. Future studies are needed to further examine the potential of NAV in the treatment of colon cancer.
在本研究中，我们研究了黑曼巴蛇全毒液（NAV）对人结肠癌细胞的抗增殖活性。NAV诱导的抗增殖作用与S期细胞周期停滞以及亚G0/G1 DNA含量的细胞数量增加有关，这被认为是细胞凋亡的一个标志。通过膜联蛋白V/PI染色也证实了细胞凋亡。此外，流式细胞术分析显示线粒体膜电位丧失，同时细胞色素c和Smac/DIABLO蛋白含量增加。这些效应与caspase-9和caspase-3的激活以及PARP裂解有关。此外，在经NAV处理的HCT116中观察到抗凋亡Bcl-2蛋白的磷酸化。总之，我们的研究首次记录了NAV在结肠癌细胞中的抗增殖/促凋亡作用。我们的结果强烈表明线粒体参与了NAV诱导的癌细胞凋亡。未来需要进一步研究NAV在结肠癌治疗中的潜力。
