alpha-Amanitin is the principal toxin of several deadly poisonous mushrooms, exerting its toxic function by inhibiting RNA-polymerase II.
Alpha-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]. Alpha-Amanitin dramatically decreases the expression of gap junctional genes (Gja1, Gja4 and Gjc1) and FSHr and LHr in cumulus cells[4].
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].
References:
[1]. Zhao J, et al. Pathological effects of the mushroom toxin alpha-amanitin on BALB/c mice. Peptides. 2006 Dec;27(12):3047-3052.
[2]. Kume K, et al. α-Amanitin Restrains Cancer Relapse from Drug-Tolerant Cell Subpopulations via TAF15. Sci Rep. 2016 May 16;6:25895
[3]. Kaya E, et al. Evaluation and comparison of alpha- and beta-amanitin toxicity on MCF-7 cell line. Turk J Med Sci. 2014;44(5):728-32
[4]. Park MW, et al. RNA Polymerase II Inhibitor, α-Amanitin, Affects Gene Expression for Gap Junctions and Metabolic Capabilities of Cumulus Cells, but Not Oocyte, during in vitro Mouse Oocyte Maturation. Dev Reprod. 2013 Mar;17(1):63-72