Dacarbazine

Dacarbazine is a DNA alkylating prodrug that is activated by P450 enzymes in liver microsomes.¹ Following activation, it is converted, through a series of reactions, into a methyldiazonium cation that alkylates DNA at all phases of the cell cycle and induces apoptosis. In vitro, dacarbazine inhibits the growth of B16/F1, A-875, and SK-MEL-5 melanoma and non-cancerous WI-38 lung fibroblast and L-02 hepatocyte cell lines (IC₅₀s = 260, 287, 380, 526, and 367 μM, respectively).² Dacarbazine toxicity to 518A2 and SK-MEL-28 melanoma cell lines increases in a time-dependent manner with IC₅₀ values of 121 and >400 μM, respectively, following a 1 hour incubation and 2.5 and 50 μM, respectively, following a 96 hour incubation.³ In vivo, dacarbazine (70 mg/kg, once every 2 days) decreases tumor volume by 59.1% in a B16/F1 murine melanoma model in mice.² Formulations containing dacarbazine have been used in the treatment of metastatic melanoma and for Hodgkin's lymphoma in combination with other antineoplastic agents.

WARNING This product is not for human or veterinary use.

1. Marchesi, F., Turriziani, M., Tortorelli, G., et al. Triazene compounds: Mechanism of action and related DNA repair systems. Pharmacol. Res. 56(4), 275-287 (2007).

2. Jin, J.-l., Gong, J., Yin, T.-j., et al. PTD4-apoptin protein and dacarbazine show a synergistic antitumor effect on B16-F1 melanoma in vitro and in vivo. Eur. J. Pharmacol. 654(1), 17-25 (2011).

3. Valiahdi, S.M., Heffeter, P., Jakupec, M.A., et al. The gallium complex KP46 exerts strong activity against primary explanted melanoma cells and induces apoptosis in melanoma cell lines. Melanoma Res. 19(5), 283-293 (2009).