Staurosporin, a small kinase inhibitor, is an alkaloid derived from the bacterium Streptomyces staurosporeus.[1] Staurosporine can block the ATP-binding site of the enzimes and induce apoptosis by activation of caspase-3 in higher eukaryotes.[2]
In vitro experiment it shown that treatment with 50 nM of Staurosporin, there is a single-cell migration of breast carcinoma cells on plastic, fibronectin, or laminin surfaces.[1] Staurosporine killed Acanthamoeba trophozoites in a dose dependent way with IC50 and IC90 values of 0.265?±?0.057 and 1.27?±?0,007?μg/mL, respectively.[2] In vitro, treatment with a low concentration (10(-7) M) of staurosporine in cultured rat astrocytes, there is a significantly increased proportion of early apoptotic cells after regeneration in a staurosporine free medium. However, treatment with a higher (10(-6) M) concentration of staurosporine, there is further obviously increased necroptosis after regeneration in a staurosporine free medium.[3] In vitro efficacy test it indicated that 1 μM STS was able to activate the autophagy pathway in SH-SY5Y cells.[4] In addition, treatment with 5 to 50 μM of staurosporine, conidial cell viability decreased in a concentration-dependent manner, suggesting that staurosporine has potent antifungal activity against N. crassa conidia.[5]
In vivo efficacy study it demonstrated that mice were treated with 3 mg/kg staurosporine via oral gavage twice a week has no effects on tumor growth. But mice were treated with the combination of 3 mg/kg staurosporine and 50 mg/kg lapatinib inhibited the tumor growth obviously.[6]
References:
[1].Meyer FAH, et al. The Presence of Yin-Yang Effects in the Migration Pattern of Staurosporine-Treated Single versus Collective Breast Carcinoma Cells. Int J Mol Sci. 2021 Nov 4;22(21):11961.
[2].Cartuche L, et al. Staurosporine from Streptomyces sanyensis activates Programmed Cell Death in Acanthamoeba via the mitochondrial pathway and presents low in vitro cytotoxicity levels in a macrophage cell line. Sci Rep. 2019 Aug 12;9(1):11651.
[3].?imenc J, et al. Staurosporine induces apoptosis and necroptosis in cultured rat astrocytes. Drug Chem Toxicol. 2012 Oct;35(4):399-405.
[4].Brunelli F, et al. PINK1 Protects against Staurosporine-Induced Apoptosis by Interacting with Beclin1 and Impairing Its Pro-Apoptotic Cleavage. Cells. 2022 Feb 15;11(4):678.
[5].Castro A, et al. Rotenone enhances the antifungal properties of staurosporine. Eukaryot Cell. 2010 Jun;9(6):906-14.
[6].Zambrano JN, et al. Staurosporine, an inhibitor of hormonally up-regulated neu-associated kinase. Oncotarget. 2018 Nov 13;9(89):35962-35973.
Staurosporin 是一种小激酶抑制剂,是一种从细菌 Streptomyces staurosporeus 中提取的生物碱。[1] Staurosporine 可以阻断酶的 ATP 结合位点,并通过激活 caspase-3 诱导细胞凋亡在高等真核生物中。[2]
体外实验表明,50 nM Staurosporin 处理后,乳腺癌细胞在塑料、纤连蛋白或层粘连蛋白表面出现单细胞迁移。[1] Staurosporine 杀死棘阿米巴滋养体呈剂量依赖性,IC50 和 IC90 值分别为 0.265 ± 0.057 和 1.27 ± 0,007 μg/mL。[2] 在体外,用低浓度 (10(-7) M) 处理在培养的大鼠星形胶质细胞中,星形胶质细胞在不含星形胶质细胞的培养基中再生后,早期凋亡细胞的比例显着增加。然而,用更高（10(-6) M）浓度的星形孢菌素处理,在无星形孢菌素培养基中再生后坏死性凋亡进一步明显增加。[3]体外药效试验表明,1 μM STS 能够激活 SH-SY5Y 细胞的自噬途径。[4] 此外,用 5 至 50 μM 星形孢菌素处理后,分生孢子细胞活力呈浓度依赖性下降,表明星形孢菌素对 N. crassa 分生孢子具有有效的抗真菌活性。[5]
体内功效研究表明,每周两次通过口服强饲法以 3 mg/kg 星形孢菌素处理小鼠对肿瘤生长没有影响。但小鼠用 3 mg/kg 星形孢菌素和 50 mg/kg 拉帕替尼联合治疗可明显抑制肿瘤生长。[6]