Mastoparan, a peptide toxin from wasp venom, induces stimulation of phosphoinositide breakdown with an EC50 value of 9μM[1]. Mastoparan accelerates guanosine-5'-3-O-thiotriphosphate binding and consequent GTP-binding regulatory protein (G protein) activation in part by enhancing the dissociation of bound GDP[2]. Mastoparan has been widely used in anti-inflammatory studies and as a model compound to develop related derivatives[3].
In vitro, Mastoparan exhibited an anticancer towards Hep-G2 cells with IC50=189.59±0.6µg/ml after 24h treatment[4]. Treatment with 25μM Mastoparan for 8h significantly induced cell death in Jurkat T leukemia cells and normal peripheral blood cells[5]. Mastoparan treatment at 20μM within 1min significantly induced a rapid increase in cytosolic-free Ca2+ concentration elevation in Tobacco BY-2 cells[6].
In vivo, Mastoparan treatment via a peritumor route at 5 mg/kg/day for 5 consecutive days inhibited the tumor growth in the murine melanoma model[7]. The combination therapy of gemcitabine (60mg/kg/day) and Mastoparan (6mg/kg/day) for 14 days via intraperitoneal injection significantly inhibited tumor progression in a mouse model of breast cancer[5].
References:
[1] Gusovsky F, Soergel D G, Daly J W. Effects of mastoparan and related peptides on phosphoinositide breakdown in HL-60 cells and cell-free preparations[J]. European Journal of Pharmacology: Molecular Pharmacology, 1991, 206(4): 309-314.
[2] Higashijima T, Uzu S, Nakajima T, et al. Mastoparan, a peptide toxin from wasp venom, mimics receptors by activating GTP-binding regulatory proteins (G proteins)[J]. Journal of Biological Chemistry, 1988, 263(14): 6491-6494.
[3] Chen X, Zhang L, Wu Y, et al. Evaluation of the bioactivity of a mastoparan peptide from wasp venom and of its analogues designed through targeted engineering[J]. International journal of biological sciences, 2018, 14(6): 599.
[4] Elsharkawy A M, Galhom R A, Amin B H, et al. In Vitro Evaluation of Some Therapeutic Applications of Wasp Venom and Mastoparan[J]. Egyptian Academic Journal of Biological Sciences. A, Entomology, 2024, 17(1): 121-130.
[5] Hilchie A L, Sharon A J, Haney E F, et al. Mastoparan is a membranolytic anti-cancer peptide that works synergistically with gemcitabine in a mouse model of mammary carcinoma[J]. Biochimica Et Biophysica Acta (BBA)-Biomembranes, 2016, 1858(12): 3195-3204.
[6] Takahashi K, Isobe M, Muto S. Mastoparan induces an increase in cytosolic calcium ion concentration and subsequent activation of protein kinases in tobacco suspension culture cells[J]. Biochimica et Biophysica Acta (BBA)-Molecular Cell Research, 1998, 1401(3): 339-346.
[7] de Azevedo R A, Figueiredo C R, Ferreira A K, et al. Mastoparan induces apoptosis in B16F10-Nex2 melanoma cells via the intrinsic mitochondrial pathway and displays antitumor activity in vivo[J]. Peptides, 2015, 68: 113-119.
Mastoparan是一种来源于黄蜂毒液的肽类毒素，可刺激磷酸肌醇分解，EC50值为9μM[1]。Mastoparan通过促进结合态GDP的解离，加速鸟苷-5'-3-O-硫代三磷酸结合并激活GTP结合调节蛋白（G蛋白）[2]。Mastoparan被广泛应用于抗炎研究，并作为开发相关衍生物的模型化合物[3]。
在体外，Mastoparan处理24小时对Hep-G2细胞表现出抑制作用（IC50=189.59±0.6µg/ml）[4]。25μM浓度的Mastoparan处理8小时可显著诱导Jurkat T白血病细胞和正常外周血细胞死亡[5]。20μM浓度的Mastoparan在1分钟内即可引起烟草BY-2细胞胞浆游离Ca2+浓度快速升高[6]。
在体内，连续5天经瘤周途径给药施用5mg/kg/day剂量的Mastoparan，可抑制小鼠黑色素瘤模型的肿瘤生长[7]。吉西他滨（60mg/kg/day）与Mastoparan（6mg/kg/day）联合腹腔注射治疗14天，能显著抑制乳腺癌小鼠模型的肿瘤进展[5]。