[en] 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.
Disciplines :
Pharmacy, pharmacology & toxicology
Author, co-author :
Bonjean, Karine ; Université de Liège - ULiège > Département des sciences précliniques MI > Histologie - Cytologie
De Pauw-Gillet, Marie-Claire ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Histologie - Cytologie - Département des sciences biomédicales et précliniques
Quetin-Leclercq, Joëlle
Angenot, Luc ; Université de Liège - ULiège > Département de pharmacie > Pharmacognosie
Bassleer, Roger ; Université de Liège - ULiège > Relations académiques et scientifiques (Médecine)
Language :
English
Title :
In Vitro Cytotoxic Activity of Two Potential Anticancer Drugs Isolated from Strychnos: Strychnopentamine and Usambarensine
Publication date :
1996
Journal title :
Anticancer Research
ISSN :
0250-7005
eISSN :
1791-7530
Publisher :
International Institute of Anticancer Research, Greece
Leclercq J, De Pauw-Gillet M-Cl, Bassleer R and Angenot L: Screening of cytotoxic activities of Strychnos alkaloids (methods and results). J Ethnopharmacol 15: 305-316, 1986.
Quetin-Leclercq J, De Pauw-Gillet M-Cl, Angenot L and Bassleer R: Effects of strychnopentamine on cells cultured in vitro Chem-Biol Interact 80: 203-216, 1991.
Quetin-Leclercq J, Bouzahzah B, Pons A, Greimers R, Angenot L, Bassleer R and Barbason H: Strychnopentamine, a potential anticancer agent. Planta Med 59: 59-62, 1993.
Bjorkman A and Phillips-How ard PA: Drug-resistant malaria: mechanisms of development and interferences for malaria control. Trans R Soc Trop Med Hyg 84: 323-324, 1990.
Guerrant RL: The global problem of amoebiasis; current status. research needs and opportunity for progress. Rev Infect Dis 8: 218-227, 1986.
Boreham PFL: Giardiasis and its control. Pharm J. August 31, 271-274,1991
Wright CW, Bray DH, O'Neill MJ, Warhurst DC, Phillipson JD, Quetin-Leclercq J and Angenot L: Antiamoebic and antiplasmodial activities of alkaloids isolated from Strychnos usambarensis. Planta Med 57: 337-340, 1991.
Wright CW, Allen D, Cai Y, Chen Z, Phillipson JD, Kirby GC, Warhurst DC, Tits M and Angenot L: Selective antiprotozoal activity of some Strychnos alkaloids. Phytother Res 8: 149-152, 1994.
Quetin-Leclercq J, Dupont L, Wright CW, Phillipson JD, Warhurst DC and Angenot L. Modélisation moléculaire de l'usambarensine, de la tubulosine et de l'émćtine, alcaloides cytotoxiques et antiamibiens. J Pharm Belg 46: 2, 85-92, 1991.
Grollman AP: Emetine: new uses for an old drug. The Ohio State Med J 66: 257-259, 1970.
Gupta RS, Krepinsky JJ and Simmovitch L. Structural determinants responsible for the biological activity of (-)emetinc, (-)cryptoplcurine and (-)tylocrebine structure-activity relationship among related compounds. Mol Pharmacol 19: 136-143, 1980.
Angenot L and Bisset NG: Isolement et structure de nouveaux alcaloïdes extraits du Strychnos usambarensis. Gilg du Rwanda J Pharm Belg 5: 585-588, 1971.
Angenot L, Coune C and Tits M: Nouveaux alcaloides des feuilles du Strychnos usambarensis. J Pharm Belg 33: 1, 11-23, 1978.
Bessis M: Cellules du sang normal et pathologique. Ed, Masson et Cie. Paris, 1972.
Schweighoffer T, Schweighoffer E, Apati A, Antoni F, Molnar G, Lapis K and Banfalvi G: Cytometric analysis of DNA replication inhibited by emetine and cyclosporin A. Histochemistry 96: 93-97, 1991.
Lambertz M, Coucke P, Bouvier J, De Pauw-Gillet M-Cl and Bassleer R: Characterization of two mouse B16 melanoma clones, pigmented or non pigmented. Eur Arch Biol 103: 239-244, 1992.
Reasor MJ: A review of the biology and toxicologic implications of the induction of lysosomal lamellar bodies by drugs. Toxicol Appl Pharm 97: 47-56, 1989.
Pisha E, Chai H, Lee I, Chagwedera TE, Farnsworth NR, Cordell GA, Beecher CWW, bong HHS, Kinghorn AD, Brown DM, Wam MC, Wall ME, Hieken TJ, Das Gupta TK and Pezzuto JM: Discovery of betulinic acid as a selective inhibitor of human melanoma that functions by induction of apoptosis. Nature Medicine 1: 10, 1046-1051, 1995.
Urabe K, Aroca P, Tsukamoto K, Mascagna D, Palumbo A, Prota G and Hearing VJ: The inherent cytotoxicity of melanin precursors' a revision. Biochim Biophys Acta 1221: 272-278, 1994.
Horvath S: Cytotoxicity of drugs and diverse chemical agents to cell cultures. Toxicology 16: 59-66, 1980.
Isomaa B, Lilius H and West A: Evaluation of cytotoxicity of the first twenty MEIC chemicals by using haemolysis of human erythrocytes as an endpoint. ATLA- Altern lab anim 20: 226-229, 1992.
Grollman AP and Jarkovsky Z: Emetine and related alkaloids. In: JW Corcoran and F.E. Hahn (eds.), Antibiotics Vol 3 Springer Verlag, Berlin. 1974, pp 420-435.
