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Antitumor activities of Sphaerococccus coronopifolius bromoditerpenes on in vitro human cancer cell lines

Celso Alves1, 2, Joana Silva1, Rebeca Alvariño3, Eva Alonso3, Rafaela Freitas1, Susete G. Pinteus1, Helena Gaspar1, 4, Amparo Alfonso3, Luis M. Botana3 and Rui P. Pedrosa1*
  • 1 MARE – Marine and Environmental Sciences Centre, ESTM, Polytechnic Institute of Leiria, Portugal
  • 2 University of Aveiro, Biology Department, Do*Mar Doctoral Programme on Marine Science, Technology and Management, Portugal
  • 3 Facultad de Veterinaria, Universidad de Santiago de Compostela, Department of Pharmacology, Spain
  • 4 Faculdade de Ciências, Universidade de Lisboa, BioISI - Biosystems & Integrative Sciences Institute, Portugal

The marine organisms have revealed to be an attractive source of new compounds with a great diversity of chemical structures. These compounds can be used as scaffolds for the design and development of new drugs with great effectiveness and specificity to human diseases, such as cancer. The red alga Sphaerococcus coronopifolius demonstrated to be an interesting source of brominated cyclic diterpenes. However, few studies were accomplished to characterize their antitumor potential and the activated intracellular signaling pathways. Therefore, the main goal of this work was to study the antitumor potential of five bromoditerpenes isolated from S. coronopifolius (Sphaerococcenol A, 12R-hydroxy-bromosphaerol, 12S-hydroxy-bromosphaerol, Sphaerodactylomelol and Bromosphaerol) on several in vitro human cancer cell lines. Compounds were purified by HPLC and identified by NMR and MS techniques. The cytotoxic activity of bromoditerpenes was evaluated on several tumor cell lines, obtained from distinct tissues (SH-SY5Y; MCF-7; A549, NCI-H226, PC-3, HCT-15; CACO-2; SK-MEL-28) to define their selectivity and potency. Cells were treated with different concentrations of compounds (0.1-100 µM) during 24h, and the results revealed by the MTT assay. Apoptotic mechanisms were studied through the analysis of the mitochondrial membrane potential, Caspase-9 activity and DNA condensation/ fragmentation by DAPI staining. The compounds exhibited an IC50 range between 5µM to 95µM, with Sphaerococcenol A exhibiting the highest cytotoxicity. The treatment of MCF-7 cells with the bromoditerpenes induced changes in the mitochondrial membrane potential, increased Caspase-9 activity, and promoted DNA condensation and fragmentation. In conclusion, S. coronopifolius bromoditerpenes exhibited interesting cytotoxic activities, which seems to be linked with apoptosis. Thus, it is of the utmost importance to characterize the associated intracellular signaling pathways to define their effective pharmacological potential.

Acknowledgements

Authors would like to acknowledge the financial support of the Portuguese Foundation for Science and Technology (FCT) through Strategic Project UID/MAR/04292/2013 granted to MARE, Red2Discovery Project (PTDC/MAR-BIO/6149/2014), co-financed by COMPETE (POCI-01-0145-FEDER-016791), Oncologia de Precisão: Terapias e Tecnologias Inovadoras Project (POINT4PAC) (SAICTPAC/0019/2015 - LISBOA-01-0145-FEDER-016405) and PhD grant conceded to CA (SFRH/BD/97764/2013).

References

Keywords: Red algae, Cancer, Apoptosis, bioactive compounds, Natural Products

Conference: IMMR'18 | International Meeting on Marine Research 2018, Peniche, Portugal, 5 Jul - 6 Jul, 2018.

Presentation Type: Oral Presentation

Topic: Blue Biotech

Citation: Alves C, Silva J, Alvariño R, Alonso E, Freitas R, Pinteus SG, Gaspar H, Alfonso A, Botana LM and Pedrosa RP (2019). Antitumor activities of Sphaerococccus coronopifolius bromoditerpenes on in vitro human cancer cell lines. Front. Mar. Sci. Conference Abstract: IMMR'18 | International Meeting on Marine Research 2018. doi: 10.3389/conf.fmars.2018.06.00162

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Received: 27 Jul 2018; Published Online: 07 Jan 2019.

* Correspondence: PhD. Rui P Pedrosa, MARE – Marine and Environmental Sciences Centre, ESTM, Polytechnic Institute of Leiria, Peniche, Portugal, rpedrosa@ipleiria.pt