Searching for innovative antitumoral drugs in marine microalgae

Kamberovic, Farah

http://hdl.handle.net/10400.1/13994

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Authors

Kamberovic, Farah

Advisor(s)

Barreira, Luísa

Viegas, Carla

Abstract(s)

Cancer is one of the leading causes of death globally. Current available chemotherapeutics are aggressive and not specific to cancer cells, causing damage and death of healthy cells as well. As a consequence, the number of side-effects in patients arise. Another important therapeutic issue is the development of resistance and/or development of secondary malignancies. In some types of cancer, such as hepatocellular carcinoma (HCC) and acute monocytic leukaemia (AML), chemotherapy is associated with high mortality rate. This points out to the need to search and identify new sources of anti-cancer drugs with high selectivity and toxicity only for malignant cells, while conserving healthy cells. Marine microalgae are a rich source of different bioactive metabolites (e.g. poly-unsaturated fatty acids, carotenoids, polysaccharides, phenols, sterols, vitamins) with anti-inflammatory, anti-bacterial, anti-diabetic and anti-hypertensive properties, among others. During the past few years, marine microalgae have been featured in cancer research. In this research, we studied the cytotoxic effect of six selected microalgae species against adherent (HepG2) and suspended (THP-1) human cancer cell lines. The ethanolic extract of Phaeodactylum tricornutum was the most bioactive with an IC50 of 19.4±2.2 μg/mL for HepG2 cells. In addition, this extract was highly selective for HepG2 cells (SI=4.40) in comparison with a non-tumoural derived cell line (S17). The active extract was further subjected to bio-guided fractionation process to obtain four fractions: hexane, dichloromethane, ethyl-acetate and water with ethanol. Among these fractions, the dichloromethane fraction displayed high cytotoxicity towards both HepG2 and THP-1 cell lines with IC50 of 27.5±1.6 and 22.3±1.8 μg/mL, and selectivity of SI>4.54 and SI>5.60, respectively. In order to tentatively identify compounds responsible for the observable cytotoxic effect, the dichloromethane fraction was analysed by gas chromatography – mass spectrometry (GC/MS). Thirteen molecules with potential anti-cancer properties were identified, belonging to six different classes of metabolites: saturated fatty acids (SFA), polyunsaturated fatty acids (PUFAs), sterols, vitamins (dl-α-Tocopherol), phenols and terpenoid alcohols. The most abundant compounds detected were hexadecanoic acid, 9-hexadecenoic acid and 5,8,11,14,17-Eicosapentaenoic acid (EPA).