Calyculin A is a potent inhibitors of protein phosphatases 1 (PP1) and phosphatases 2A (PP2A), with IC50 values of 2nM and 0.5–1.0nM, respectively[1]. Calyculin A is a major cytotoxic compound isolated from the Japanese marine sponge Discodermia calyx[2]. Ascribed to the specific and potent inhibition of PP1 and PP2A, Calyculin A is widely used for evaluating intracellular signal transduction[3] and cancer research[4].
Calyculin A (10nM; 6h) treatment can induce inhibition of PP1 and PP2A activities and changes in immunoreactivity of PP1c and PP2Ac in MCF7 cells[5]. Calyculin A (1nM; 1h) stimulated TNF-α transcriptional activity and increased the expression of TNF-α in MC3T3-E1 cells[6].
Calyculin A (0.8μg/kg) significantly enhanced the positive inotropy and improved the diastolic function of left ventricle by increasing stroke work, cardiac output, stroke volume, ejection fraction, the slope of the left ventricular end-systolic P-V relationship (Ees) and by decreasing the slope of the left ventricular end- diastolic P-V relationship (Eed) in rats[7].
References:
[1]. Ishihara H, Martin BL, Brautigan DL, et al. Calyculin A and okadaic acid: inhibitors of protein phosphatase activity. Biochem Biophys Res Commun. 1989 Mar 31;159(3):871-7. doi: 10.1016/0006-291x(89)92189-x. PMID: 2539153.
[2]. Wakimoto T, Egami Y, Abe I. Calyculin: Nature's way of making the sponge-derived cytotoxin. Nat Prod Rep. 2016 Jun 2;33(6):751-60. doi: 10.1039/c5np00123d. PMID: 26923942.
[3]. Antaraki A, Ang KL, Antoni FA. Involvement of calyculin A inhibitable protein phosphatases in the cyclic AMP signal transduction pathway of mouse corticotroph tumour (AtT20) cells. Br J Pharmacol. 1997 Jul;121(5):991-9. doi: 10.1038/sj.bjp.0701228. PMID: 9222558; PMCID: PMC1564779.
[4]. Edelson JR, Brautigan DL. The Discodermia calyx toxin calyculin a enhances cyclin D1 phosphorylation and degradation, and arrests cell cycle progression in human breast cancer cells. Toxins (Basel). 2011 Jan;3(1):105-19. doi: 10.3390/toxins3010105. Epub 2011 Jan 24. PMID: 22069692; PMCID: PMC3210456.
[5]. Favre B, Turowski P, Hemmings BA. Differential inhibition and posttranslational modification of protein phosphatase 1 and 2A in MCF7 cells treated with calyculin-A, okadaic acid, and tautomycin. J Biol Chem. 1997 May 23;272(21):13856-63. doi: 10.1074/jbc.272.21.13856. PMID: 9153244.
[6]. Qiu L, Yoshida K, Amorim BR, et al. Calyculin A stimulates the expression of TNF-alpha mRNA via phosphorylation of Akt in mouse osteoblastic MC3T3-E1 cells. Mol Cell Endocrinol. 2007 Jun 15;271(1-2):38-44. doi: 10.1016/j.mce.2007.03.005. Epub 2007 Apr 4. PMID: 17482757.
[7]. HUANG Hui-li, XIE Ming, GAO Li, et al. Studies on hemodynamic effects of Calyculin A of protein phosphatase 1 and 2A inhibitor and its underlying mechanism in rats. Chinese Pharmacological Bulletin, 2018, 34(12): 1697-1702.
Calyculin A是蛋白磷酸酶1（PP1）和蛋白磷酸酶2A（PP2A）的强效抑制剂, IC50值分别为2nM和0.5–1.0nM[1]。Calyculin A是从日本海绵Discodermia calyx中分离出的主要细胞毒性化合物[2]。由于对蛋白磷酸酶1和蛋白磷酸酶2A的特异性和强效抑制，Calyculin A被广泛用于评估细胞内信号转导[3]和癌症研究[4]。
Calyculin A （10nM；6小时）处理可以抑制PP1和PP2A活性，并改变MCF7细胞中PP1c和PP2Ac的免疫反应性[5]。Calyculin A （1nM；1小时）可以刺激TNF-α转录活性并增加MC3T3-E1细胞中TNF-α的表达[6]。
Calyculin A （0.8μg/kg）处理显著增强了正性肌力作用，并通过增加搏功、心输出量、搏出量、射血分数、左心室收缩末期压力-容积关系曲线的斜率（Ees）和降低左心室舒张末期压力-容积关系曲线的斜率（Eed）来改善大鼠左心室的舒张功能[7]。