Haemanthamine

Haemanthamine is a crinine-type alkaloid isolated from the Amaryllidaceae plants with potent anticancer activity. Haemanthamine targets ribosomal that inhibits protein biosynthesis during the elongation stage of translation. Haemanthamine has pro-apoptotic, antioxidant, antiviral, antimalarial and anticonvulsant activities[1][2].

Haemanthamine (1-100 µM; 24-48 hours; A2780 cells) treatment shows a time- and dose-dependent decrease in cell viability[2].Haemanthamine (10 µM; 24-72 hours; A2780 cells) treatment leads to a significant inhibition of A2780 cell proliferation[2].Haemanthamine binds at the A-site cleft of the peptidyl transferase center on the large ribosomal subunit, creating unique molecular interactions with the 25S rRNA. Haemanthamine has a highly specific inhibitory effect on pre-rRNA processing, leading to the activation of a p53-dependent antitumoral surveillance pathway known as nucleolar stress[1].

A pharmacokinetic study of Haemanthamine in rats shows a rapid distribution phase of 30 min, a half-life of 70.4 min, and a major clearance through renal elimination. The high distribution volume of 13.7 L/kg suggests a high intracellular penetration, and its plasmatic concentration remains higher than 1 μM for at least 1 hr after a single 10-mg/kg administration[1].

[1]. Pellegrino S, et al. The Amaryllidaceae Alkaloid Haemanthamine Binds the Eukaryotic Ribosome to Repress Cancer Cell Growth. Structure. 2018 Mar 6;26(3):416-425.e4.
[2]. SeifrtovÁ M, et al. Haemanthamine alters sodium butyrate-induced histone acetylation, p21WAF1/Cip1 expression, Chk1 and Chk2 activation and leads to increased growth inhibition and death in A2780 ovarian cancer cells. Phytomedicine. 2017 Nov 15;35:1-10.