Rottlerin, a natural product purified from Mallotus Philippinensis, is a specific PKC inhibitor, with IC50 values for PKCδ of 3-6 μM, PKCα,β,γ of 30-42 μM, PKCε,η,ζ of 80-100 μM. Rottlerin acts as a direct mitochondrial uncoupler, and stimulates autophagy by targeting a signaling cascade upstream of mTORC1. Rottlerin induces apoptosis via caspase 3 activation[2]. Rottlerin inhibits HIV-1 integration and Rabies virus (RABV) infection.IC50 & Target:IC50: 3-6 μM (PKCδ), 30-42 μM (PKCα,β,γ), 80-100 μM (PKCε,η,ζ).In Vitro:Rottlerin (20 μM, 2/6/24 hours) dramatically decreases the cyclin D-1 mRNA levels in a time-dependent manner in primary HMVEC[2].
Rottlerin (20 μM) exhibits cell proliferation in HMVEC[2].
In Vivo:Rottlerin (20 mg/kg, gavage 5 days per week, once daily, for 6 weeks) inhibits AsPC-1 pancreatic tumor growth in Balb C nude mice with no toxicity.
Rottlerin inhibits tumor cell proliferation, and induces apoptosis through activation of caspase-3 and cleavage of poly(ADP-ribose) polymerase (PARP).