Author(s)

Gabriela Gambato, Érico G. Baroni, Charlene S. C. Garcia, Rafaele Frassini, Caroline O. S. Frozza, Sidnei Moura, Cláudio M. P. Pereira, Mutue T. Fujii, Pio Colepicolo, Ana Paula F. Lambert, João A. P. Henriques, Mariana Roesch-Ely

Botanical Institute, SMA, São Paulo, Brazil.
Faculty of Pharmacy, University of Caxias do Sul, Caxias do Sul, Brazil.
Institute of Chemistry and Geosciences, Federal University of Pelotas, Pelotas, Brazil.
Institute of Chemistry, University of São Paulo, São Paulo, Brazil.
Laboratory of Biotechnology of Natural and Synthetic Products, Biotechnology Institute, University of Caxias do Sul, Caxias do Sul, Brazil.
Laboratory of Genomics, Proteomics and DNA Repair, Biotechnology Institute, University of Caxias do Sul, Caxias do Sul, Brazil.

Marine algae have been used as food since ancient times and today are consumed as a regular part of the diet. In this study, we hypothesized that H. grandifolius phlorotannins-enriched extract exerts cytotoxic selective effects against tumor cell lines promoting cell death trough apoptosis mechanisms. The aim of the present study is to characterize chemically and investigate the selective cytotoxic effect of the H. grandifolius extract on epithelial tumour cell lines (A375, A549, Hep-2, HeLa) compared to non-malignant cell line (Hek-293), and evaluate possible molecular mechanisms involved in the programmed cell death pathway. High-resolution directly-infusion mass spectrometry (HR-DIMS) analysis with electrospray ionization (ESI) was performed in positive and negative mode. Cytotoxicity was evaluated through colorimetric assay and morphological alterations were observed in giemsa stained cells after extract treatment. Apoptosis was further evaluated by annexin V staining. Spectra showed peaks m/z between 370 and 430 and molecular formula was defined upon isotopic ratio. Extract showed selectivity to the non-tumor line with enhanced cytotoxicity in tumor cells according to the concentration and exposure time. After 72 h treatment, the HeLa strain was more susceptible to the extract, followed by lines Hep2, A375 and A549. Morphological changes by giemsa were observed after increased doses of extracts and staining for annexin V showed majority of tumor cells at early stages of the apoptotic process. Here, selective anti-tumor activity of extract taken from the alga H. grandifolius was able to suppress proliferation and promote apoptosis-mediated cell death with induction of initial stages of apoptosis in different cell lines.

Algae; Cytotoxicity; Apoptosis; Cancer; in Vitro

Gambato, G. , Baroni, É. , Garcia, C. , Frassini, R. , Frozza, C. , Moura, S. , Pereira, C. , Fujii, M. , Colepicolo, P. , Lambert, A. , Henriques, J. and Roesch-Ely, M. (2014) Brown Algae Himantothallus grandifolius (Desmarestiales, Phaeophyceae) Suppresses Proliferation and Promotes Apoptosis-Mediated Cell Death in Tumor Cells. Advances in Biological Chemistry, 4, 98-108. doi: 10.4236/abc.2014.42014.