Tong-ngam Pirut, Roytrakul Sittiruk, Sritanaudomchai Hathaitip
Institute of Molecular Biosciences, Nakhon Pathom, Thailand E-mail :
Asian Pac J Cancer Prev. 2015;16(7):2807-11. doi: 10.7314/apjcp.2015.16.7.2807.
Scorpion venom peptides recently have attracted attention as alternative chemotherapeutic agents that may overcome the limitations of current drugs, providing specific cytotoxicity for cancer cells with an ability to bypass multidrug-resistance mechanisms, additive effects in combination therapy and safety. In the present study, BmKn-2 scorpion venom peptide and its derivatives were chosen for assessment of anticancer activities. BmKn-2 was identified as the most effective against human oral squamous cells carcinoma cell line (HSC-4) by screening assays with an IC50 value of 29 μg/ml. The BmKn-2 peptide killed HSC-4 cells through induction of apoptosis, as confirmed by phase contrast microscopy and RT-PCR techniques. Typical morphological features of apoptosis including cell shrinkage and rounding characteristics were observed in treated HSC-4 cells. The results were further confirmed by increased expression of pro-apoptotic genes such as caspase-3, -7, and -9 but decrease mRNA level of anti-apoptotic BCL-2 in BmKn-2 treated cells, as determined by RT-PCR assay. In summary, the BmKn-2 scorpion venom peptide demonstrates specific membrane binding, growth inhibition and apoptogenic activity against human oral cancer cells.
蝎毒肽最近作为一种替代化疗药物引起了人们的关注，它可能克服现有药物的局限性，对癌细胞具有特异性细胞毒性，能够绕过多药耐药机制，在联合治疗中具有相加作用且安全性良好。在本研究中，选择了BmKn-2蝎毒肽及其衍生物来评估其抗癌活性。通过筛选试验，BmKn-2被确定为对人口腔鳞状细胞癌细胞系（HSC-4）最有效的，其IC50值为29μg/ml。BmKn-2肽通过诱导凋亡杀死HSC-4细胞，相差显微镜和RT-PCR技术证实了这一点。在处理过的HSC-4细胞中观察到了凋亡的典型形态学特征，包括细胞收缩和变圆。RT-PCR分析确定，在BmKn-2处理的细胞中，促凋亡基因如caspase-3、-7和-9的表达增加，但抗凋亡BCL-2的mRNA水平降低，进一步证实了上述结果。总之，BmKn-2蝎毒肽对人口腔癌细胞具有特异性膜结合、生长抑制和凋亡诱导活性。
