Shikonin Derivative DMAKO-05 Inhibits Mouse Melanoma Cell B16F0 Via AKT Signal Inhibition

Melanoma is a malignant tumor derived from melanocyte.Malignant melanoma remains the most lethal skin cancers because of its early imperceptible metastatic dissemination and aggressive growth speed.To date,development of medicines with higher therapeutic efficiency and low toxicity are important for the clinic treatment of malignant melanoma.Shikonin is the major active ingredient of traditional Chinese herb Lithospermum erythrorhizon.Its naphthaquinone structure is proved to have cytotoxicity but with poor selectivity.DMAKO-05 is a new oxime derivative of shikonin.Previous studies showed that its cytotoxicity against tumor cells was significantly higher than normal cells.So far,the anti-tumor mechanism of DMAKO-05 has been unknown.In this study,we evaluated the effect of DMAKO-05 on mouse melanoma cell 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.Akt is a key gene promoting cell proliferation,inhibiting apoptosis,and is generally highly activated in melanoma.DMAKO-05 significantly attenuated the Akt signal.DMAKO-05 also activated the mitochondrial apoptosis pathway,induced apoptosis.Collectively,DMAKO-05 had a strong cytotoxicity in B16F0 cells via inhibiting Akt activation,triggering caspase-dependent apoptosis pathway.DMAKO-05 might serve as a potential candidate compound for melanoma.