Butantan Institute, Laboratory of Genetics, Sao Paulo, SP, Brazil.
Expert Opin Investig Drugs. 2011 Sep;20(9):1189-200. doi: 10.1517/13543784.2011.602064.
Selective anticancer cell activity for both cell-penetrating and cationic antimicrobial peptides has previously been reported. As crotamine possesses activities similar to both of these, this study investigates crotamine's anticancer toxicity in vitro and in vivo.
In vitro cancer cell viability was evaluated after treatment with 1 and 5 μg/ml of crotamine. In vivo crotamine cytotoxic effects in C57Bl/6J mice bearing B16-F10 primary cutaneous melanoma were tested, with two groups each containing 35 mice. The crotamine-treated group received 1 μg/day of crotamine per animal, subcutaneously which was well tolerated; the untreated group received a placebo.
Crotamine at 5 μg/ml was lethal to B16-F10, Mia PaCa-2 and SK-Mel-28 cells and inoffensive to normal cells. In vivo crotamine treatment over 21 days significantly delayed tumor implantation, inhibited tumor growth and prolonged the lifespan of the mice. Mice in the crotamine-treated group survived at significantly higher rates (n = 30/35) than those in the untreated group (n = 7/35) (significance calculated with the Kaplan-Meier estimator). The average tumor weight in the untreated group was 4.60 g but was only about 0.27 g in the crotamine-treated mice, if detectable.
These data warrant further exploration of crotamine as a tumor inhibition compound.
先前已有报道称，某些既能穿透细胞又具有阳离子抗菌活性的细胞穿透肽具有选择性抗癌细胞活性。由于克肽具有与这两种物质相似的活性，因此本研究旨在体外和体内研究克肽的抗癌毒性。
用 1 和 5 μg/ml 的克肽处理后，评估体外癌细胞活力。在携带 B16-F10 原发性皮肤黑色素瘤的 C57Bl/6J 小鼠中测试体内克肽细胞毒性作用，每组各有 35 只小鼠。克肽治疗组每天每只动物接受 1 μg 的克肽皮下注射，耐受良好；未治疗组接受安慰剂。
5 μg/ml 的克肽对 B16-F10、Mia PaCa-2 和 SK-Mel-28 细胞具有致死作用，而对正常细胞无影响。21 天的体内克肽治疗显著延迟肿瘤植入、抑制肿瘤生长并延长了小鼠的寿命。克肽治疗组的小鼠存活率明显高于未治疗组（n = 30/35 对 n = 7/35）（用 Kaplan-Meier 估计器计算显著性）。未治疗组的平均肿瘤重量为 4.60 克，但在接受克肽治疗的小鼠中，如果可检测到，则仅约为 0.27 克。
这些数据证明克肽作为肿瘤抑制化合物值得进一步研究。
