ABSTRACT
Title
Two marine sesterterpenoids induce apoptosis in human carcinoma cells
Authors
D. De Stefano1, G. Tommonaro2, S. De Rosa2, G. Kroemer3, M.C. Maiuri1, R. Carnuccio1
1Dept. of Experimental Pharmacology, University of Naples Federico II, Via D. Montesano, 49, 80131-Naples, Italy;
2National Research Council – Institute of Biomolecular Chemistry,Via Campi Flegrei, 34 – 80078 Pozzuoli (Naples), Italy
3INSERM U848, Institut Gustave Roussy, 29 rue C. Desmoulins, Villejuif 94805, France.
1Dept. of Experimental Pharmacology, University of Naples Federico II, Via D. Montesano, 49, 80131-Naples, Italy;
2National Research Council – Institute of Biomolecular Chemistry,Via Campi Flegrei, 34 – 80078 Pozzuoli (Naples), Italy
3INSERM U848, Institut Gustave Roussy, 29 rue C. Desmoulins, Villejuif 94805, France.
Abstract
Apoptosis, a form of programmed cell death, is a critical defence mechanism against the formation and progression of cancer and acts by eliminating potentially deleterious cells without causing such adverse effects, as inflammatory response and ensuing scar formation1. Therefore, targeting apoptotic pathways becomes an intriguing strategy for the development of chemotherapeutic agents1. In last decades, marine natural products, such as sesterterpenoids, have played an important role in the discovery and development of new drugs 2. Interestingly, many of these compounds have a strong potential as anticancer drugs by inhibiting cell proliferation and/or inducing cell death2. In the present study, weinvestigated the effects of scalaradial and cacospongionolide, two sesterterpenoidsfrom Cacospongia scalaris andFasciospongia cavernosa marine sponge, onthe apoptotic signalling pathway in threedifferent human tumoral cells. The T47D (human breast carcinoma), HeLa (human cervix carcinoma) and HCT116 (human colon carcinoma) cells were incubated for 24 h with scalaradial (10 μM) or cacospongionolide (10 μM). DNA fragmentation, comet assay and quantification of the mitochondrial transmembrane potential (Δ Ψm) were performed as previously described;3-5 apoptosis array was carried out in agreement with manufacturer instructions. Treatment of T47D cells with scalaradial or cacospongionolidefor 24 h brought about a significant increase in DNA migration as well as fragmentation. Moreover, incubation of HCT116 and HeLa cells with scalaradial or cacospongionolide for 24 h caused an increased expression of pro-apoptotic proteins. Finally, scalaradial or cacospongionolide, added to HCT116 and HeLa cells overnight, induced a significant and concentration-dependent loss of mitochondrial transmembrane potential, an early apoptosis signalling event. In conclusion, scalaradial and cacospongionolide, by determining human cancer cell apoptosis, may represent new promising compounds to inhibit cancer cell proliferation.
1Lin X, Liu M, Hu C, Liao DJ. Targeting cellular proapoptotic molecules for developing anticancer agents from marine sources. Curr Drug Targets. 2010;11(6):708-15.
2De Rosa S.and Mitova M. Bioactive marine sesterterpenoids” in Studies in Natural Products Chemistry, Ed. Atta-ur-Rahman, Elsevier, Amsterdam, Netherlands 2005; Vol. 32, pp 109-168.
3D'Acquisto F, de Cristofaro F, Maiuri MC, Tajana G, Carnuccio R. Protective role of nuclear factor kappa B against nitric oxide-induced apoptosis in J774 macrophages. Cell Death Differ. 2001; 8(2):144-51.
4Balasubramanyam M, Adaikalakoteswari A, Sameermahmood Z, Mohan V. Biomarkers of oxidative stress: methods and measures of oxidative DNA damage (COMET assay) and telomere shortening. Methods Mol Biol. 2010;610:245-61.
5Zamzami N., Marchetti P., Castedo M., Decaudin D., Macho A., Hirsh T., Susin S. A., Petit P. X., Mignotte B., Kroemer G. Sequential reduction of mitochondrial transmembrane potential and generation of reactive oxygen species in early programmed cell death. J Exp Med., 1995 182:367-377.
1Lin X, Liu M, Hu C, Liao DJ. Targeting cellular proapoptotic molecules for developing anticancer agents from marine sources. Curr Drug Targets. 2010;11(6):708-15.
2De Rosa S.and Mitova M. Bioactive marine sesterterpenoids” in Studies in Natural Products Chemistry, Ed. Atta-ur-Rahman, Elsevier, Amsterdam, Netherlands 2005; Vol. 32, pp 109-168.
3D'Acquisto F, de Cristofaro F, Maiuri MC, Tajana G, Carnuccio R. Protective role of nuclear factor kappa B against nitric oxide-induced apoptosis in J774 macrophages. Cell Death Differ. 2001; 8(2):144-51.
4Balasubramanyam M, Adaikalakoteswari A, Sameermahmood Z, Mohan V. Biomarkers of oxidative stress: methods and measures of oxidative DNA damage (COMET assay) and telomere shortening. Methods Mol Biol. 2010;610:245-61.
5Zamzami N., Marchetti P., Castedo M., Decaudin D., Macho A., Hirsh T., Susin S. A., Petit P. X., Mignotte B., Kroemer G. Sequential reduction of mitochondrial transmembrane potential and generation of reactive oxygen species in early programmed cell death. J Exp Med., 1995 182:367-377.