Microalgal compounds modulate carcinogenesis in the gastrointestinal tract Helena M. Amaro 1, 2 , Rita Barros 3 , A. Catarina Guedes 1 , I. Sousa-Pinto 1, 4 , and F. Xavier Malcata 1, 5 1 Interdisciplinary Centre for Marine and Environmental Research (CIIMAR/CIMAR), Rua dos Bragas no. 289, P-4050-123 Porto, Portugal 2 Institute of Biomedical Sciences Abel Salazar (ICBAS), Rua Jorge Viterbo Ferreira no. 228, P-4050-313 Porto, Portugal 3 Institute of Pathology and Molecular Immunology of the University of Porto (IPATIMUP), Rua Dr Roberto Frias s/n, P-4200-465 Porto, Portugal 4 Faculty of Sciences, University of Porto (FCUP), Rua do Campo Alegre s/n, P-4169-007 Porto, Portugal 5 Department of Chemical Engineering, University of Porto, Rua Dr Roberto Frias s/n, P-4200-465 Porto, Portugal Gastrointestinal cancers rank second in overall cancer- related deaths. Carotenoids, sulfated polysaccharides, and polyunsaturated fatty acids (PUFAs) from microal- gae exhibit cancer chemopreventive features at different stages of carcinogenesis. For instance, sulfated polysac- charides bear a prophylactic potential via blocking ad- hesion of pathogens to the gastric surface, whereas carotenoids are effective against Helicobacter pylori in- fection. This effect is notable because H. pylori has been targeted as the primary cause of gastric cancer. Recent results on antitumor and antibacterial compounds syn- thesized by microalgae are reviewed here, with an em- phasis on their impact upon H. pylori infection and derived pathologies accompanying the progression of gastric carcinogenesis. Microalgal-derived compounds Microalgae harbor specialized enzymes – these enzymes have allowed microalgae to adapt to specific living condi- tions during the course of evolution. Microalgae can indeed grow in a wide variety of environments from freshwater to extremely saline waters [1]. Microalgae possess an extra competitive advantage associated with metabolic plastici- ty; depending on their current physiological state, their secondary metabolism may be triggered by several forms of externally applied stress [2]. Moreover, microalgal compounds respond to a wide diversity of molecular targets with a marked selectivity – thus raising a potential pharmaceutical interest [3], for example, as antioxidants, antivirals, anti-inflammatories, antimicrobials, and antitumor agents. They have also garnered attention for their food potential, as antioxidants and antimicrobial additives. Several of the aforementioned compounds are polysaccharides, carotenoids, or unsaturat- ed long chain fatty acids bearing chemical structures not found elsewhere – or which are present at much higher concentrations than in other natural sources [1]. However, microalgae remain, to date, largely unexplored and unexploited, so they represent a unique opportunity to obtain novel or known metabolites at low cost. Antitumor compounds Cancer is presently the largest single cause of death in men and women worldwide, and its global incidence has dou- bled in the latest decade [4]. Cancer follows an imbalance in the rates of cell proliferation and apoptosis – where the latter is the natural mechanism for removal of damaged and malfunctioning cells. Apoptosis involves proteins from different families, such as Bcl-2, Bax, and caspases 3, 6, 7, 8, and 9; these are engaged in complex signal transduction pathways and may affect tumor growth at one or more stages of carcinogenesis [1]. A variety of compounds from natural sources have proven beneficial against cancer growth, for example, fla- vonoids, phenolic acids, and carotenoids [5]. The underly- ing mechanisms of tumor suppression often involve inhibition of tumor cell-mediated protease activity [6], attenuation of tumor-induced angiogenesis, promotion of cell cycle arrest [7,8], induction of apoptosis [9], and im- munostimulation [10]. Chemoprevention – defined as the use of biological or chemical agents (natural or synthetic) to reverse, suppress, or prevent carcinogenic progression of invasive cancer – is a promising anticancer approach aimed at reducing mor- bidity and mortality [11]. In an ideal scenario, chemo- preventive agents should come from natural sources, and be capable of inducing growth arrest or apoptosis in cancer cells without affecting their healthy counterparts [12]. Antitumor capacity of microalgal carotenoids Antioxidants, such as carotenoids found in several micro- algae, have antitumor properties [13]. When used in asso- ciation with the chemotherapy agent 5-fluorouracil, those metabolites facilitated complete remission in colorectal cancer, rather than partial remission as observed when chemotherapy was done in the absence of additional Review Corresponding author: Malcata, F.X. (fmalcata@fe.up.pt) 92 0167-7799/$ – see front matter ß 2012 Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.tibtech.2012.11.004 Trends in Biotechnology, February 2013, Vol. 31, No. 2