title: In vitro cytotoxic activity of two potential anticancer drugs isolated from Strychnos: strychnopentamine and usambarensine.
abstract: The cytotoxicity and the selective antiprotozoal activity of some Strychnos alkaloids, namely strychnopentamine (SP) and usambarensine (US) (7) led us to analyze and compare their effects with emetine (EM) by using mouse B16 melanoma cells cultivated in vitro. We observed by cytological analysis and proliferation rate studies that these substances induce analogous cytotoxic effects in B16 cells, but at different concentrations i.e. formation of lamellar bodies in the cytoplasm, the which contain pre-melanosomes in the case of SP and US, vacuoles and blebs. At concentrations near their respective IC50, SP and US, but not EM, decreased colony formation. We showed by incorporation of labelled precursors that SP and US first inhibit RNA synthesis while EM initially acts on protein synthesis. These alkaloids increased melanin synthesis. Furthermore, only EM and SP caused hemolysis of sheep red blood corpuscles. This could explain why the rate of antiplasmodial activity is higher for SP and EM.
authors.affiliation: Department of Histology and Cytology, University of Liège, Belgium.
authors.forename: K A
authors.initials: KA
authors.lastname: Bonjean
authors.forename: M C
authors.initials: MC
authors.lastname: De Pauw-Gillet
authors.forename: J
authors.initials: J
authors.lastname: Quetin-Leclercq
authors.forename: L
authors.initials: L
authors.lastname: Angenot
authors.forename: R J
authors.initials: RJ
authors.lastname: Bassleer
mesh_terms: D000470:Alkaloids / Q000494:pharmacology*; D000818:Animals; D018906:Antineoplastic Agents, Alkylating / Q000494:pharmacology*; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D004354:Drug Screening Assays, Antitumor; D004640:Emetine / Q000494:pharmacology; D004912:Erythrocytes / Q000187:drug effects; D006461:Hemolysis; D007211:Indoles / Q000494:pharmacology*; D008546:Melanoma, Experimental / Q000188:drug therapy / Q000473:pathology; D051379:Mice; D008853:Microscopy / Q000379:methods; D055095:Optics and Photonics; D013329:Structure-Activity Relationship
chemical_list: D000470:Alkaloids; D018906:Antineoplastic Agents, Alkylating; D000972:Antineoplastic Agents, Phytogenic; D007211:Indoles; C070902:usambarensine; C045110:strychnopentamine; D004640:Emetine