Cell lines

Rat (C6) and two human gliomas (T98G and U138MG), glial cells, Rat lung microvascular endothelial cells, Rat primary pulmonary artery endothelial cells

Preparation method

The solubility of this compound in DMSO is > 10 mM. General tips for obtaining a higher concentration: Please warm the tube at 37 ℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months.

Reacting condition

24 h

Applications

Rottlerin (24 h) decreased the growth of C6, T98G, and U138MG cells (IC50, 12 μM for C6 and >20 μM for T98G and Ui 38MG, respectively). Rottlerin (48 h) decreased the growth of C6, T98G, and Ui 38MG cells with the IC50 of 5, 7, and 9 μM, respectively. Rottlerin (5 μM) significantly reduced the number of S-phase cells in C6, T98G, and U138MG. In C6 cells, rottlerin treatment resulted in an accumulation of cytoplasmic vacuoles and packaging of cellular components within membranes. Rottlerin (5 μM) produced obvious DNA laddering in HL-60 human leukemia cells. Rottlerin dose-dependently increased basal endothelial monolayer permeability in rat LMVEC and PAEC. Rottlerin caused actomyosin filament and focal adhesion disruption.

Rottlerin was originally identified as an inhibitor of PKCδ (IC50 = 3 μM), but can also inhibit CAM kinase III and a wide range of protein kinases, including PRAK and MAPKAP-K2 (IC50s = 1.9 and 5 μM, respectively).[1],[2] It can act as a direct mitochondrial uncoupler, and stimulates autophagy by targeting a signaling cascade upstream of mTORC1.[3] Rottlerin has also been shown to have neuroprotective effects in an MPTP animal model of Parkinson’s disease.[4]

Reference:

[1]. McGovern, S.L., and Shoichet, B.K. Kinase inhibitors: Not just for kinases anymore Journal of Medicinal Chemistry 46, 1478-1483 (2003).
[2]. Davies, S.P., Reddy, H., Caivano, M., et al. Specificity and mechanism of action of some commonly used protein kinase inhibitors Biochem. J. 351(1), 95-105 (2000).
[3]. Balgi, A.D., Fonseca, B.D., Donohue, E., et al. Screen for chemical modulators of autophagy reveals novel therapeutic inhibitors of mTORC1 signaling PLoS One 4(9), 1-15 (2009).
[4]. Zhang, D., Anantharam, V., Kanthasamy, A., et al. Neuroprotective effect of protein kinase Cδ inhibitor rottlerin in cell culture and animal models of Parkinson’s disease Journal of Pharmacology and Experimental Therapeutics 322(3), 913-922 (2007).