Cacospongionolide and scalaradial, two marine sesterterpenoids as potent apoptosis-inducing factors in human carcinoma cell lines

• Published in: PloS one 2012-04, Vol.7 (4), p.e33031
• Main Authors: De Stefano, Daniela, Tommonaro, Giuseppina, Malik, Shoaib Ahmad, Iodice, Carmine, De Rosa, Salvatore, Maiuri, Maria Chiara, Carnuccio, Rosa
• Format: Article
• Language: English
• Subjects: 4-Butyrolactone - analogs & derivatives; 4-Butyrolactone - pharmacology; Active Transport, Cell Nucleus - drug effects; Animals; Antineoplastic agents; Antineoplastic Agents - pharmacology; Antineoplastic drugs; Antitumor agents; Apoptosis; Apoptosis - drug effects; Apoptosis Regulatory Proteins - metabolism; Apoptosis-inducing factor; Aquatic Organisms - chemistry; Biology; Breast cancer; Breast carcinoma; Cacospongia; Cancer; Cancer therapies; Carcinoma; Cell death; Cell Line, Tumor; Cell migration; Cell Nucleus - drug effects; Cell Nucleus - metabolism; Cell proliferation; Cell Proliferation - drug effects; Cell Survival - drug effects; Cervical carcinoma; Cervix; Chemistry; Chemotherapy; Colon; Colon cancer; Councils; Cystic fibrosis; Cytotoxicity; Defense programs; Deoxyribonucleic acid; Development and progression; Development strategies; DNA; DNA fragmentation; DNA Fragmentation - drug effects; Drug development; Drugs; Earth Sciences; Fasciospongia; Fragmentation; Homosteroids - pharmacology; Humans; Inflammation; Inflammatory response; Medicine; Membrane potential; Metabolites; Microscopy; Mitochondria; Morphology; Natural products; NF-kappa B p50 Subunit - metabolism; NF-κB protein; Oxidative stress; Porifera - chemistry; Proteins; Pyrans - pharmacology; Sesterterpenes - pharmacology; Sesterterpenoids; Signal transduction; Signaling; Transcription Factor RelA - metabolism; Tumor cell lines; Viability
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0033031

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 formation. Therefore, targeting apoptotic pathways becomes an intriguing strategy for the development of chemotherapeutic agents. In last decades, marine natural products, such as sesterterpenoids, have played an important role in the discovery and development of new drugs. Interestingly, many of these compounds have a strong potential as anticancer drugs by inhibiting cell proliferation and/or inducing cell death. In the present study, we investigated the effects of scalaradial and cacospongionolide, two sesterterpenoids from Cacospongia scalaris and Fasciospongia cavernosa marine sponges, on the apoptotic signalling pathway in three different human tumoral cells. Results were obtained by using DNA fragmentation, comet and viability assays, quantification of the mitochondrial transmembrane potential and Western blot. The T47D (human breast carcinoma), A431 (human epidermoid carcinoma), HeLa (human cervix carcinoma) and HCT116 (human colon carcinoma) cells were incubated for 24 h with scalaradial or cacospongionolide. Treatment of T47D cells with scalaradial or cacospongionolide for 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. Furthermore, 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. These effects paralleled with those achieved with p50 and p65, NF-κB subunits, nuclear level. In conclusion, scalaradial and cacospongionolide, by determining human cancer cell apoptosis, may represent new promising compounds to inhibit cancer cell proliferation.