Mitotic Block of Human Blood Cells by Vinca herbacea, Catharanthus roseus and Colchicine Alkaloids


Department of plant Cell Biology, Saveh branch, Islamic Azad University, Saveh, Iran


Catharanthus roseus (L.) G.Don is a plant which produces anticancer and anti-mitotic indole alkaloids. Colchicine is an anti-mitotic drug. Anti-mitotic effects of Vinca herbacea Waldst. & Kit. indole alkaloids is unknown. The study were evaluated the antimitotic effect of alkaloids of V. herbacea, Catharanthus roseus andcolchicineon mitosis and microtubule arrangement of human blood cells. In this research, alkaloids were extracted from V. herbacea (herba)and C. roseus (rose). In vitro anti-mitotic and microtubule shortening effects of different concentration of these alkaloids and colchicine were studied on peripheral blood cells. Three alkaloids include herba alkaloid (V. herbacea alkaloid) and rose alkaloid (C. roseus alkaloid) and colchicine, especially herba alkaloid with increasing concentrations (0, 5, 10 and 20 µ that induced mitotic block at the metaphase to anaphase transition. Mitotically blocked cells were exhibited aberrant spindles by microtubule dynamics suppression. All three alkaloids strongly suppresses the rate and extent of microtubule shortening in vitro. Our results showed V. herbacea are a novel source of anti-mitotic and anticancer compounds, probably better of C. roseus.


1. Van Der Heijden R, Jacobs DI, Snoeijer W, Hallard D, Verpoorte R. The Catharanthus alkaloids: Pharmacognosy and biotechnology. Curr Med Chem. 2004;11:1241-1253.

2. Boğa M, Kolak U, Topçu G, Bahadori F, Kartal M, Farnsworth NR. Two new indole alkaloids from Vinca herbacea L. Phytochemistry Let. 2011;4:399-403.

3. Almagro L, Fernández-Pérez F, Pedreño MA. Indole Alkaloids from Catharanthus roseus: Bioproduction and Their Effect on Human Health (Review).Molecules. 2015;20:2973-3000.

4. Pyuskyulev B, Ognyanov I, Panov P. Alkaloids of Vinca herbacea. Tetrahedron Let. 1967;8:4559-62.

5. Aynilian GH, Farnswor NR, Trojakek J. Alkaloids of Vinca species: Isolation and characterization of indole alkaloids from V. libanotica. J Nat Prod. 1974;37:299-308.

6. Ebrahimzadeh H, Ataei Azimi A, Noori-Dafoi MR. The distribution of indole alkaloids of C. roseus G. Don. Daru. 1996;6:17- 30.

7. Gagua N, Baghdikian B, Mabrouki F, Elias R, Vachnadze V, Bakuridze A. HPLC determination of majdine in Vinca herbacea. Nat. Prod. Commun. 2011;6:1831-1834.

8. Gulcin I, Beydemir S, Topal F, Gagua N, Bakuridze A, Bayram R. Apoptotic, antioxidant and antiradical effects of majdine and isomajdine from Vinca herbacea. J Enzyme Inhib Med Chem. 2012;27:587-94.

9. Moudi M, Go R, Yien CYS, Nazre M. Vinca Alkaloids. Int J Prev Med. 2013;4:1231-1235.

10. Jordan MA, Wilson L. Microtubules as a target for anticancer drugs. Nat Rev Cancer. 2004;4:253-265.

11. Safarzadeh E, Sandoghchian S, Baradaran B. Herbal medicine as inducers of apoptosis in cancer treatment (Review). Adv Pharm Bull. 2014;4:421-427.

12. Park IH, Lerou PH, Zhao R, Huo H, Daley GQ. Generation of human-induced pluripotent stem cells. Nat Protoc. 2008;3:1180-1186.

13. Renaudin JP. Reversed- phase High- performance liquid chromatographic. J Chromat. 1984;291:165-174.

14. Miura Y, Hirata K, Kurano N. Formation of rose alkaloid in multiple shoot of Catharanthus roseus. Planta Med. 1987;50:18-20.

15. Moorhead PS, Nowell PC, Mellmam WJ, Battips DM, Hungerford DA. Chromosome preparations of leukocytes cultured from human peripheral blood. Exp Cell Res. 1960;20:613-616.

16. Nowell PC. Mitotic inhibition and chromosome damage by mitomycine in Human Leukocytes Cultures. Exp. Cell Res. 1964;33:445- 449.

17. Silva TL, Silva MIA, Venancio LPR, Zago CES, Moscheta VAG, Lima AVB. Simple method for culture of peripheral blood lymphocytes of Testudinidae. Genet Mol Res. 2011;10:3020-3025.

18. Ataei Azimi A, Delnavaz Hashemloian B, Ebrahimzadeh H, Majd A. High in vitro production of ant-canceric indole alkaloids from periwinkle (Catharanthus roseus) tissue culture. African J Biotechn. 2008;7:2834-2839.

19. Jean-Decoster C, Brichese L, Barret J, Tollon Y, Kruczynski A, Hill B. Vinflunine, a new Vinca alkaloid: cytotoxicity, cellular accumulation and action on the interphasic and mitotic microtubule cytoskeleton of PtK2 cells. Anti-Cancer Drugs. 1999;10:537-543.

20. Hadfield JA, Lawrence NJ, Mcgown AT. Tubulin as a target for anticancer drugs: Agents which interact with the mitotic spindle. Med Res Rev. 1998;18:259-296.

21. Gigant B, Wang C, Ravelli RB, Roussi F, Steinmetz MO, Curmi PA. Structural basis for the regulation of tubulin by vinblastine. Nature. 2005;435:519-522.

22. Daly EM, Taylor RE. Entropy and enthalpy in the activity of tubulin-based antimitotic agents. Curr Chem Bio. 2009;l3:47–59.

23. Sertel S, Fu Y, Zu Y, Rebacz B, Konkimalla B, Plinkert PK. Molecular docking and pharmacogenomics of Vinca alkaloid and their monomeric precursor, vindoline and catharanthine. Biochem Pharmacol. 2011;81:723-735.

24. Coderch C, Morreale A, Gago F. Tubulin-based structure-affinity relationship for antimitotic Vinca alkaloid. Anticancer Agents Med Chem. 2012;12:219-225.

25. Tsvetkov FO, Kulikova AA, Devred F, Zernii E, Lafitte D, Makarov AA. Thermodynamics of calmodulin and tubulin binding to the Vinca-alkaloid vinorelbine. Mol Biol. 2011;45:697-702.

26. Barbier P, Tsvetkov PO, Breuzard G, Devred F. Deciphering the molecular mechanism of anti-tubulin plant derived drugs. Phytochem Rev. 2013;13:157-169.