Institute of Nanoscience and Nanotechnology (INN), National Atomic Energy Commission (CNEA), National Scientific and Technical Research Council (CONICET), Constituyentes Node, Av. General Paz 1499, (B1650KNA) San Martín, Buenos Aires, Argentina.
Biological Research Institute, National Council of Scientific and Technique Research (IIB-CONICET), Funes 3250 7600, Mar del Plata, Argentina; National University of Mar del Plata, School of Science, 7600 Mar del Plata, Argentina.
Bioorg Med Chem Lett. 2021 Jun 1;41:127959. doi: 10.1016/j.bmcl.2021.127959. Epub 2021 Mar 22.
Solanum tuberosum aspartic Proteases (StAPs) show selective plasma membrane permeabilization, inducing cytotoxicity of cancer cells versus normal cells in vitro. Herein, we aimed to evaluate both StAP3 systemic toxicity and antitumoral activity against human melanoma in vivo. The toxicity of a single high dose of StAP3 (10 µg/g body weight, intraperitoneally) was assessed in a Balb/c mice model. Subcutaneous A375 human melanoma xenografts in athymic nude (nu/nu) mice were induced. Once tumors developed (mean larger dimension = 3.8 ± 0.09 mm), mice were StAP3-treated (6 µg/g body weight, subcutaneously under the tumor at a single dose). For both models, controls were treated with physiologic saline solution. StAP3-treated mice showed a significant inhibition of tumor growth (p < 0.05) compared with controls. No signs of toxicity were detected in StAP3-treated mice in both models. These results suggest the potential of these plant proteases as anticancer agents.
马铃薯天冬氨酸蛋白酶（StAPs）显示出对细胞膜的选择性通透性，在体外能诱导癌细胞对正常细胞的细胞毒性。在此，我们旨在评估 StAP3 的全身毒性和体内对人黑色素瘤的抗肿瘤活性。在 Balb/c 小鼠模型中评估了 StAP3 的单次高剂量（10μg/g 体重，腹腔内注射）的毒性。在无胸腺裸鼠（nu/nu）中诱导皮下 A375 人黑色素瘤异种移植瘤。一旦肿瘤形成（平均最大尺寸=3.8±0.09mm），即用 StAP3 治疗（6μg/g 体重，在肿瘤下单次皮下给药）。对于这两种模型，对照组均用生理盐水处理。与对照组相比，StAP3 治疗组的肿瘤生长受到显著抑制（p<0.05）。在这两种模型中，StAP3 治疗组的小鼠均未出现毒性迹象。这些结果表明这些植物蛋白酶具有作为抗癌剂的潜力。
