Cannabidiol induces cytotoxicity and cell death via apoptotic pathway in cancer cell lines

Biomolecules and Therapeutics

Volumn 16, Issue 2, 2008, Pages 87-94

  Choi, Won Hyung ^a   Park, Hyun Do ^b   Baek, Seung Hwa ^c   Chu, Jong Phil ^a   Kang, Mae Hwa ^a   Mi, Yu Jing ^a  

^a Kyung Hee University Hospital   (South Korea)

^b Yonsei University College of Dentistry   (South Korea)

^c Wonkwang University   (South Korea)

Author keywords

Breast cancer cells; Cannabidiol; Caspase; Cytotoxicity; LDH release

Indexed keywords

ANTINEOPLASTIC AGENT; CANNABIDIOL; CASPASE 3; CASPASE 8; CASPASE 9; LACTATE DEHYDROGENASE;

ANIMAL CELL; ANIMAL CELL CULTURE; APOPTOSIS; ARTICLE; BREAST CANCER; CANCER CELL CULTURE; CANCER INHIBITION; CELL DEATH; CELL VIABILITY; COLON CANCER; CONTROLLED STUDY; CYTOTOXICITY; DOSE RESPONSE; ENZYME ACTIVATION; ENZYME ACTIVITY; ENZYME RELEASE; FIBROBLAST; HUMAN; HUMAN CELL; HUMAN CELL CULTURE; IN VITRO STUDY; KIDNEY CANCER; LUNG CANCER; MELANOMA B16; MOUSE; NONHUMAN;

EID: 69549105763     PISSN: 19769148     EISSN: None     Source Type: Journal    
DOI: 10.4062/biomolther.2008.16.2.087     Document Type: Article

References (35)

1. Andersson, D., Liu, J. J., Nilsson, A. and Duan, R. D. (2003). Ursolic acid inhibits proliferation and stimulates apoptosis in HT29 cells following activation of alkaline sphingomyelinase. Anticancer Res. 23, 3317-3322. (Pubitemid 36975429)
2. Asakawa, Y. (1995). "In Progress in the Chemistry of Organic Natural Products"; Herz, W., Kirby, G. W., Moore, R. E., Steglich, W. and Tamm, C. eds. Springer: Vienna, Vol : 65.
3. Bold, R. J., Termuhlen, P. M. and McConkey, D. J. (1997). Apoptosis, cancer and cancer therapy. Surg Oncol. 6, 133-142.
4. Buja, L. M., Eigenbrodt, M. L. and Eigenbrodt, E. H. (1993). Apoptosis and necrosis. Basic types and mechanisms of cell death. Arch Pathol Lab Med. 117, 1208-1214.
5. Buttke, T. M. and Sandstrom, P. A. (1994). Oxidative stress as a mediator of apoptosis. Immunol Today. 15, 7-10.
6. Carrier, E. J., Auchampach, J. A., and Hillard, C. J. (2006). Inhibition of an equilibrative nucleoside transporter by cannabidiol: a mechanism of cannabinoid immuno-suppression. Proc Natl Acad Sci U S A. 103, 7895-7900.
7. Casanova, M. L., Blazquez, C., Martinez-Palacio, J., Villanueva, C., Fernandez-Acenero, M. J., Huffman, J. W., Jorcano, J. L. and Guzman, M. (2003). Inhibition of skin tumor growth and angiogenesis in vivo by activation of cannabinoid receptors. J Clin Invest. 111, 43-50. (Pubitemid 36134847)
8. Chiang, L. C., Ng, L. T., Chiang, W., Chang, M. Y. and Lin, C. C. (2003). Immunomodulatory activities of flavonoids, monoterpenoids, triterpenoids, iridoid glycosides and phenolic compounds of Plantago species. Planta Medica. 69, 600-604. (Pubitemid 37041053)
9. Consroe, P., Martin, A. and Singh, V. (1981). Antiepileptic potential of cannabidiol analogs. J. Clin. Pharmacol. 21, 428-436.
10. Consroe, P., Benedito, M. A., Leite, J. R. and Carlini, E. A., Mechoulam R. (1982). Eur J Pharmacol. 83, 293-298.
11. Esposito, G., De Filippis, D., Maiuri, M. C., De Stefano, D., Carnuccio, R. and Iuvone, T. (2006). Cannabidiol inhibits inducible nitric oxide synthase protein expression and nitric oxide production in beta-amyoid stimulated PC12 neurons through p38 MAP kinase and NF-kappaB involvement. Neurosci Lett. 399, 91-95.
12. Guimaraes, F. S., Chiaretti, T. M., Graeff, F. G. and Zuardi, A. W. (1990). Anti-anxiety effect of cannabidiol in the elevated plusmaze. Psychopharmacol (Berl). 100, 558-559.
13. Garcia-Arencibia, M., Gonzalez, S., De Lago, E., Ramos, J. A., Mechoulam, R. and Fernandez-Ruiz, J. (2007). Evaluation of the neuroprotective effect of cannabinoids in a rat model of Parkinson's disease: importance of antioxidant and cannabinoid receptor-independent properties. Brain Res. 1134, 162-170. (Pubitemid 46135535)
14. Giudice, E. D., Rinaldi, L., Passarotto, M., Facchinetti, F., D'Arrigo, A., Guiotto, A., Carbonare, M. D., Battistin, L. and Leon, A. (2007). Cannabidiol, unlike synthetic cannabinoids, triggers activation of RBL-2H3 mast cells. J Leukoc Biol. 81, 1512-1522. (Pubitemid 46827974)
15. Grub, S., Persohn, E., Trommer, W. E. and Wolf, A. (2000). Mechanisms of cyclosporine A-induced apoptosis in rat hepatocyte primary cultures. Toxicol Appl Pharmacol. 163, 209-220. (Pubitemid 30158550)
16. Hah, J. C., Rhew, T. H., Choi, E. S., Chung, H. Y. and Park, K. Y. (1992). Anti-tumor effect of ursolic acid against inbred hepatoma in CBA/J Mouse. Journal of Korean Cancer Association. 24, 790-794.
17. Harmand, P. O., Duval, R., Liagre, B., Jayat-Vignoles, C., Beneytout, J. L., Delage, C. and Simon, A. (2003). Ursolic acid induces apoptosis through caspase-3 activation and cell cycle arrest in HaCat cells. Int J Oncol. 23, 105-112.
18. Kerr, J. F. R., Wyllie, A. H. and Currie, A. R. (1972). Apoptosis: a basic biological phenomenon with wide ranging implications in tissue kinetics. British Journal of Cancer. 26, 239-257.
19. Lee, K. H., Lim, Y. M., Wu, T. S., Zhang, D. C., Yamagishi T., Hayashi T., Hall I. H., Chang J. J. and Wu R. Y. (1988). The cytotoxic principles of Prunella vulgaris, Psychotria serpens, and Hyptis capitata: ursolic acid and related derivatives. Planta Medica. 54, 308-311.
20. Ligresti, A., Moriello, A. S., Starowicz, K., Matias, I., Pisanti, S., De petrocellis, L., Laezza, C., Portella, G., Bifulco, M. and Di Marzo, V. (2006). Antitumor activity of plant cannabinoid with emphasis on the effect of cannabidiol on human breast carcinoma. J Pharmacol Exp Ther. 318, 1375-1387.
21. Martin, B. R. (1986). Cellular effects of cannabinoids. Pharmacol Rev. 38, 45-74.
22. Martin, A. R., Consroe, P., Kane, V. V., Shah, V., Singh, V., Lander, N., Mechoulam, R. and Srebnik, M. (1987). Structure-anticonvulsant activity relationships of cannabidiol analogs. NIDA Res Monogr. 79, 48-58.
23. Mckallip, R. J., Jia, W., Schlomer, J., Warren, J. W., Nagarkatti, P. S. and Nagarkatti, M. (2006). Cannabidiol-induced apoptosis in human leukemia cells: A novel role of cannabidiol in the regulation of p22phox and Nox4 expression. Mol Pharmacol. 70, 897-908. (Pubitemid 44268447)
24. Mosmann, T. (1983). Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods. 65, 55-63.
25. Nicoletti, I., Migliorati, G., Pagliacci, M. C., Grignani, F. and Riccardi C. (1991). A rapid and simple method for measuring thymocyte apoptosis by propidium iodide staining and flow cytometry. J Immunol Methods. 139, 271-279.
26. Nicholson, D. W., Ali, A., Thomberry, N. A., Vaillancourt, J. P., Ding, C. D., Gallant, M., Gareau, Y., Griffin, P. R., Labelle, M. and Lazebnik, Y. A. (1995). Identification and inhibition of the ICE/CED-3 protease necessary for mammalian apoptosis. Nature. 376, 37-43.
27. Perry, N. B., Forster, L. M., Lorimer, S. D., May, B. C. and Weavers, R. T. (1996). Isoprenyl phenyl ethers from liverworts of the genus Trichocolea: cytotoxic activity, structural corrections, and synthesis. J. Nat. Prod. 59, 729-733.
28. Pertwee, R. G. (1997). Pharmacology of cannabinoid CB1 and CB2 receptors. Pharmacol Ther. 74, 129-180.
29. Shishodia, S., Majumdar, S., Banerjee, S. and Aggarwal, B. B. (2003). Ursolic acid inhibits nuclear factor-kappaB activation induced by carcinogenic agents through suppression of IkappaBalpha kinase and p65 phosphorylation: correlation with down-regulation of cyclooxygenase 2, matrix metalloproteinase 9, and cyclin D1. Cancer Res. 63, 4375-4383. (Pubitemid 36951006)
30. Soo, L. Y., Jin, D. Q., Beak, S. M., Lee, E. S. and Kim, J. A. (2003). Inhibition of ultraviolet-A-modulated signaling pathways by asiatic acid and ursolic acid in HaCaT human keratinocytes. Eur J Pharmacol. 476, 173-178.
31. Vaccani, A., Massi, P., Colombo, A., Rubino, T. and Parolaro, D. (2005). Cannabidiol inhibits human glioma cell migration through a cannabinoid receptor-independent mechanism. Br J Pharmacol. 144, 1032-1036. (Pubitemid 40593001)
32. Weiss, L., Zeira, M., Reich, S., Har-Noy, M., Mechoulam, R., Slavin, S. and Gallily, R. (2006). Cannabidiol lowers incidence of diabetes in non-obese diabetic mice. Autoimmunity. 39, 143-151. (Pubitemid 43675258)
33. Wyllie, A. H. (1992). Apoptosis and the regulation of cell numbers in normal and neoplastic tissues: an overview. Cancer Metastasis Rev. 11, 95-103.
34. Wyllie, A. H. (1985). The biology of cell death in tumours. Anticancer Res. 5, 131-136.
35. Wyllie, A. H., Kerr, J. F. and Currie, A. R. (1980). Cell death: the significance of apoptosis. Int Rev Cytol. 68, 251-306.