Browsing by Author "Botana, Luís M."
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- From marine origin to therapeutics: the antitumor potential of marine algae-derived compoundsPublication . Alves, Celso; Silva, Joana; Pinteus, Susete; Gaspar, Helena; Alpoim, Maria C.; Botana, Luís M.; Pedrosa, RuiMarine environment has demonstrated to be an interesting source of compounds with uncommon and unique chemical features on which themolecularmodeling and chemical synthesis of new drugs can be based with greater efficacy and specificity for the therapeutics. Cancer is a growing public health threat, and despite the advances in biomedical research and technology, there is an urgent need for the development of new anticancer drugs. In this field, it is estimated that more than 60% of commercially available anticancer drugs are natural biomimetic inspired. Among the marine organisms, algae have revealed to be one of the major sources of new compounds of marine origin, including those exhibiting antitumor and cytotoxic potential. These compounds demonstrated ability to mediate specific inhibitory activities on a number of key cellular processes, including apoptosis pathways, angiogenesis, migration and invasion, in both in vitro and in vivo models, revealing their potential to be used as anticancer drugs. This review will focus on the bioactive molecules from algae with antitumor potential, from their origin to their potential uses, with special emphasis to the alga Sphaerococcus coronopifolius as a producer of cytotoxic compounds.
- Sphaerococcus coronopifolius bromoterpenes as potential cancer stem celltargeting agentsPublication . Alves, Celso; Serrano, Eurico; Silva, Joana; Rodrigues, Carlos; Pinteus, Susete; Gaspar, Helena; Botana, Luís M.; Alpoim, Maria C.; Pedrosa, RuiCancer is one of the major threats to human health and, due to distinct factors, it is expected that its incidence will increase in the next decades leading to an urgent need of new anticancer drugs development. Ongoing experimental and clinical observations propose that cancer cells with stem-like properties (CSCs) are involved on the development of lung cancer chemoresistance. As tumour growth and metastasis can be controlled by tumourassociated stromal cells, the main goal of this study was to access the antitumor potential of five bromoterpenes isolated from Sphaerococcus coronopifolius red alga to target CSCs originated in a co-culture system of fibroblast and lung malignant cells. Cytotoxicity of compounds (10–500 μM; 72 h) was evaluated on monocultures of several malignant and non-malignant cells lines (HBF, BEAS-2B, RenG2, SC-DRenG2) and the effects estimated by MTT assay. Co-cultures of non-malignant human bronchial fibroblasts (HBF) and malignant human bronchial epithelial cells (RenG2) were implemented and the compounds ability to selectively kill CSCs was evaluated by sphere forming assay. The interleucine-6 (IL-6) levels were also determined as cytokine is crucial for CSCs. Regarding the monocultures results bromosphaerol selectively eliminated the malignant cells. Both 12S-hydroxy-bromosphaerol and 12R-hydroxy-bromosphaerol steroisomers were cytotoxic towards non-malignant bronchial BEAS-2B cell line, IC50 of 4.29 and 4.30 μM respectively. However, none of the steroisomers induced damage in the HBFs. As to the co-cultures, 12R-hydroxy-bromosphaerol revealed the highest cytotoxicity and ability to abrogate the malignant stem cells; however its effects were IL-6 independent. The results presented here are the first evidence of the potential of these bromoterpenes to abrogate CSCs opening new research opportunities. The 12R-hydroxy-bromosphaerol revealed to be the most promising compound to be test in more complex living models.