Shikonin Derivative DMAKO-05 Inhibits Akt Signal Activation and Melanoma Proliferation

DMAKO‐05((S)‐1‐((5E,8E)‐5,8‐bis(hydroxyimino)‐1,4‐dimethoxy‐5,8‐dihydronaphthalen‐2‐yl)‐4‐methylpent‐3‐enyl 3‐methylbutanoate) is a novel oxime derivative of shikonin, the major component extracted from Chinese herb Lithospermun erythrorhizon. Here, we report that DMAKO‐05 had an antitumor activity against mouse melanoma cell line B16F0. Our studies indicated that DMAKO‐05 not only inhibited B16F0 proliferation and migration but also led to cell cycle arrest at G1 phase and cell apoptosis, in which DMAKO‐05 triggered mitochondrial‐mediated apoptosis signal including caspase‐9/3 and PARP. In response to DMAKO‐05 treatment, the Akt‐mediated survival signals were remarkably attenuated in B16F0 cells. Collectively, DMAKO‐05 has a strong cytotoxicity in B16F0 cells via inhibiting Akt activation, inducing G1 arrest, and promoting B16F0 cell apoptosis. DMAKO‐05 might serve as a potential candidate lead compound for melanoma. The novel oxime derivative of shikonin DMAKO‐05 was found toxic to melanoma cell B16F0. DMAKO‐05 remarkably inhibited the phosphorylation of Akt, induced G1 cell cycle arrest, and promoted B16F0 melanoma cell apoptosis. DMAKO‐05 might serve as a potential inhibitor for melanoma.