α-Amanitin

α-Amanitin is the principal toxin of several deadly poisonous mushrooms, exerting its toxic function by inhibiting RNA-polymerase II. IC50 & Target:ADCs cytotoxin, RNA-polymerase II^[1] In Vitro: α-Amanitin decreases TAF15 mRNA and TAF15 protein levels in MKN45 cells, and inhibits the RNAPII activity towards TAF15 mRNA^[2]. alpha-Amanitin decreases cell viability by 14%, 21%, 41%, 44%, and 50% at concentrations of 100, 10, 1, 0.1, and 0.01 μg/mL, respectively. The LD₅₀ of the alpha-Amanitin at 36 h is measured as 1 μg/mL. The total amount of protein within the cell at 24 h is significantly increased for the 1 μg/mL dose of alpha-Amanitin compared to the control^[3]. α-Amanitin dramatically decreases the expression of gap junctional genes (Gja1, Gja4 and Gjc1) and FSHr and LHr in cumulus cells^[4]. In Vivo: The intravenous LD₅₀ dose of alpha-Amanitin is 0.327 mg/kg body weight after intravenous injection into BALB/c mice. After 12 h of alpha-Amanitin injection in caudal vein, the levels of WBC, RBC and HGB decrease significantly, while those of BUN and Crea increase significantly in serum. alpha-Amanitin inhibits some genes (Hsp90b1, Irx4, etc.), whose encoded proteins regulate the RNA polymerase II activity. alpha-Amanitin down-regulates some proteins (Nmi, Trpc5, etc.) taking part in the transcription progress^[1]. alpha-Amanitin has potent activity in DTC suppression. Mice injected with alpha-Amanitin (0.4 mg/kg, i.p.)-treated cells maintain their body weight, while those receiving a peritoneal injection of MKN45 cells show a constant decrease in body weight^[2].