Brown Algae <i>Himantothallus grandifolius</i> (Desmarestiales, Phaeophyceae) Suppresses Proliferation and Promotes Apoptosis-Mediated Cell Death in Tumor Cells

Abstract

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 altera-* Corresponding author. G. Gambato et al. 99tions 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.

The Influence of Spirulina platensis Filtrates on Caco-2 Proliferative Activity and Expression of Apoptosis-Related microRNAs and mRNA

“…The most evident changes in Caco-2 morphology, reflecting the hallmarks of cell apoptosis, were noticed at the highest concentration, i.e., 5% ( v / v ). Our observations are in good agreement with previous studies showing the cytotoxic effects of macroalgal extracts induced in breast cancer cell lines, and the series of morphological changes related to apoptosis, including cell shrinkage [35,36]. …”

Antibacterial, antioxidant and anticancer properties of Turbinaria conoides (J. Agardh) Kuetz

“…Cytotoxicity of highest concentration (80 μg/mL) was showed~2 fold higher activity Control EAF (320 µg/mL) Quercetin (160 µg/mL) than that of lower concentration (20 μg/mL). Cytotoxicity of various extract obtained from a variety algae collectively demonstrated that the brown algae have a potential source of compounds presenting biological activities on tumor cells [34]. Cytotoxicity and antioxidant activity of EAF were found to be well correlated and concentration dependent.…”

“…Other report revealed that cell cycle arrest leads to increase in sub-G0/G1cell population after treatment with increasing doses of linalool terpenoid [36]. Phlorotanninsenriched extract of brown alga of H. grandifolius exhibited cytotoxicity against tumor cell line including Hep-2 and promoting cell death trough apoptosis mechanisms [34].…”

“…In addition, the mitochondria membrane potential assay was further supported that the EAF of T. conoides inducing apoptosis in HepG2 cells. JC-1 probe is a fluorescent cationic dye that can selectively accumulate into mitochondria by electrochemical gradient and changes color from red to green as ΔΨm decreases [25][26][27][28][29][30][31][32][33][34][35].…”

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“…Statistical data revealed that TAA and cytotoxicity of S. marginatum were found to be well correlated along with concentration. Cytotoxicity of various extract obtained from a variety algae collectively demonstrated that the brown algae have a potential source of compounds presenting biological activities on tumor cells [19]. Recent report demonstrated that S. marginatum methanol extract powerfully inhibits cell proliferation of EAT and BeWo cells and less effect on non transformed HEK 293 cells.…”