Cytotoxic and cytostatic activity of erlangerins from Commiphora erlangeriana.
The resin of Commiphora erlangeriana is known to be poisonous to humans and animals and has traditionally been used as an arrow poison. Since recent phytochemical studies on this plant material has identified four major lignans (named, Erlangerins A to D) that closely relate to the structure of podophyllotoxin, it was hypothesised that the well known poisoning effect of the resin could in part be due to direct toxicity to mammalian cells. Hence, the toxicity of Erlangerins was studied by measuring the viability of two human (HeLa and EAhy926) and two murine (L929 and RAW 264.7) cell lines. As assessed by the MTT assay, the effect of Erlangerin C and D closely follow the activity profile of podophyllotoxin: they induced a concentration-dependent cytotoxicity in the murine macrophage cells (RAW 264.7) and a cytostatic effect in HeLa, EAhy926 and L929 cells. In contrast, Erlangerins A and B suppressed cell viability at relatively higher concentrations (EC(50) values higher than 3 micro M as compared with nM concentration range for Erlangerins C and D and podophyllotoxin) and their activity appears to be consistent with a cytotoxic mode of action in all cell lines studied. The structure-activity-relationship established from the study is discussed.
Habtemariam
Solomon
S
School of Chemical and Life Sciences, University of Greenwich at Medway, Central Avenue, Chatham Maritime, Kent ME4 4TB, UK. s.habtemariam@gre.ac.uk
D000818:Animals; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D029744:Commiphora / Q000737:chemistry*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D017705:Lignans / Q000737:chemistry / Q000633:toxicity*; D008264:Macrophages / Q000166:cytology / Q000187:drug effects; D015394:Molecular Structure; D014407:Tumor Cells, Cultured
D017705:Lignans