Home | About PR | Editorial board | Search | Ahead of print | Current Issue | Archives | Instructions | Subscribe | Advertise | Contact us |   Login 
Pharmacognosy Magazine
Search Article 
  
Advanced search 
 


 
 Table of Contents 
ORIGINAL ARTICLE
Year : 2018  |  Volume : 10  |  Issue : 1  |  Page : 24-30  

Algae from Portuguese Coast Presented High Cytotoxicity and Antiproliferative Effects on an In vitro Model of Human Colorectal Cancer


MARE - Marine and Environmental Sciences Centre, ESTM, Polytechnic Institute of Leiria, Leiria, Peniche, Portugal

Date of Web Publication19-Feb-2018

Correspondence Address:
Dr. Celso Alves
MARE - Marine and Environmental Sciences Centre, ESTM, Polytechnic Institute of Leiria 2520-641 Peniche
Portugal
Login to access the Email id

Source of Support: None, Conflict of Interest: None


DOI: 10.4103/pr.pr_151_16

Rights and Permissions
   Abstract 


Background: The marine environment has shown to be an interesting source of new antitumor agents, representing an important tool in cancer research. Objective: The aim of this study was to evaluate the antitumor activities of 12 algae from Peniche coast (Portugal) on an in vitro model of human colorectal cancer (Caco-2 cells). Materials and Methods: The antitumor potential was accessed by evaluating Caco-2 cell's viability and proliferation through the 3-[4, 5-dimethylthiazol-2-yl]-2, 5-diphenyl tetrazolium bromide and calcein-AM methods. Results: The dichloromethane extracts of Asparagopsis armata and Sphaerococcus coronopifolius induced the highest decrease on cell's viability (1 mg/mL; 24 h), 98.96% ± 0.39% and 98.08% ± 0.89%, respectively, followed by the methanolic extracts of S. coronopifolius (96.47% ± 1.26%) and A. armata (92.68% ± 1.17%). Regarding cell proliferation, the highest decrease of Caco-2 cell's proliferation (1 mg/mL; 24 h) was induced by the dichloromethane extract of A. armata (100% ± 0.48%), S. coronopifolius (99.04 ± 0.51%), and Plocamium cartilagineum (95.05% ± 1.19%). The highest potency was shown by the dichloromethane extract of S. coronopifolius in both, cytotoxicity and antiproliferative tests, with an IC50of 21.3 and 36.5 μg/mL, respectively. Conclusion: The extracts of A. armata and S. coronopifolius are promising sources of new bioactive molecules with application in cancer therapeutics.

Keywords: Bioactive compounds, Caco-2 cells, marine natural products, red macroalgae, seaweed


How to cite this article:
Alves C, Pinteus S, Rodrigues A, Horta A, Pedrosa R. Algae from Portuguese Coast Presented High Cytotoxicity and Antiproliferative Effects on an In vitro Model of Human Colorectal Cancer. Phcog Res 2018;10:24-30

How to cite this URL:
Alves C, Pinteus S, Rodrigues A, Horta A, Pedrosa R. Algae from Portuguese Coast Presented High Cytotoxicity and Antiproliferative Effects on an In vitro Model of Human Colorectal Cancer. Phcog Res [serial online] 2018 [cited 2020 Jul 8];10:24-30. Available from: http://www.phcogres.com/text.asp?2018/10/1/24/225812



Abbreviations Used: MTT: 3- [4, 5-dimethylthiazol-2-yl]-2, 5-diphenyl tetrazolium bromide; DMSO: Dimethyl sulfoxide; FBS: Fetal bovine serum; MEM: Minimum Essential Medium; SEM: Standard error of the mean;

SP : Sulfated polysaccharides

Summary

  • Algae from Peniche coast (Portugal) revealed to be a promising source of new bioactive compounds with potential application on cancer therapeutics.



   Introduction Top


The world's population is affected by many diseases, such as cancer, which have high social and economic impacts in all societies. This disease is one of the major public health problems worldwide with millions of new cancer patients diagnosed every year.[1] Among the different types of cancer, liver, breast, lung, stomach, and colorectal cancer present the highest mortality rates.[2] In fact, colorectal cancer is the third most frequently diagnosed, both in men and woman, and has been estimated in the US that in 2017 will occur around 135,430 of new cases and 50,260 deaths.[3] Along years, natural products have been an important source of new bioactive molecules with application in cancer therapy, and recent survey indicates that 40% of all anticancer drugs developed before 2002 are of natural products while another 20% are synthetic compounds based on natural products.[4] In the last years, as a consequence of an increasing demand for new therapeutic drugs from natural products, there is a great interest toward marine organisms. Marine organisms produce unique bioactive molecules synthesized mainly by their secondary metabolism in response to ecological pressures, such as competition for space, maintenance of unfouled surfaces, deterrence of predation, and ability to successfully reproduce.[5] The ability of these organisms live in harsh environments makes them an interesting source of novel or preexisting compounds with high value, which may provide sustainable economic and human benefits.[6],[7] In fact, the marine environment is an exceptional reservoir of bioactive natural products, many of which exhibit structural/chemical features which are not found in the terrestrial environment.[8] Among marine organisms, algae, which can be classified into green algae (Phylum Chlorophyta), red algae (Phylum Rhodophyta), and brown algae (Phylum Ochrophyta or Heterokontophyta), have triggered interest in the biomedical area, mainly due to their content on bioactive substances with great potential, including antioxidant, antimicrobial, antiviral, anthelmintic, antialgal, antiprotozoan, anti-macrofouling, anti-inflammatory, and antitumor properties.[9],[10],[11],[12]

Numerous algae extracts and metabolites have shown high cytotoxic activities; accordingly, some scientists suggest algae consumption as a chemopreventive routine against several cancers.[13],[14],[15] Different groups of bioactive molecules with antitumor activity have been isolated from algae, such as sulfated polysaccharides (SP), carotenoids, and terpenoids. Moreover, some of these compounds have shown interesting cytotoxic activities also in in vivo experimental models.[16],[17],[18],[19] Portugal has an enormous and rich marine coast. However, it continues to be mainly unexplored. The high heterogeneity along the coast provides a rich flora biodiversity. The intertidal algae flora in northern Portugal is similar to that of the coast of Central Europe (Brittany, South of British Isles), and in southern, flora is very different suffering a marked influence of Mediterranean and African species.[20],[21] Therefore, Portugal reveals excellent conditions for the discovery of novel products with high biotechnological potential, including antitumor potential. In line with this, the aim of this study was to evaluate the antitumor activities of 12 algae from Peniche coast (Portugal) on Caco-2 cells, an in vitro model of human colorectal cancer.


   Materials and Methods Top


Sampling, identification, and preparation of algae extracts

Algae were collected freshly from Peniche coast (Portugal) and immediately transported to our laboratory and identified as described in [Table 1]. Then, they were washed first in sea water followed by fresh water to remove epiphytes, sand, and other extraneous matter and stored at −80°C (Thermo, Electron Corporation). Frozen algae were mechanical reduced into a powder with a mixer grinder. To obtain algae extracts, the resulting powder was sequential extracted in 1:4 biomass: solvent ratio with methanol and dichloromethane (Fisher Scientific, United Kingdom) at constant stirring for 12 h. Liquid–liquid extraction was then performed on the methanolic extract, using n- hexane (Lab-Scan Analytical Sciences, Poland). Solvents were evaporated in a rotary evaporator (Laborota 4000, Heidolph) at 40°C and 70 rpm, and dried extracts were solubilized in dimethyl sulfoxide (Sigma-Aldrich, Germany) at 100 mg/mL. Samples were then stored at −20°C until further use.
Table 1: Algae collected from Peniche coast (Portugal) for evaluation of antitumor potential

Click here to view


Antitumor activities

Cell culture conditions

Human colorectal cancer model (Caco-2 cells) was obtained from the Leibniz Institute DSMZ – German Collection of Microorganisms and Cell Cultures and cultured in minimum essential medium (MEM) (Sigma-Aldrich, USA) supplemented with 20% of fetal bovine serum (FBS) (Hyclone, UK) and 1% of antimycotic solution (100 U/mL penicillin G, 0.25 μg/mL amphotericin B, and 100 μg/mL streptomycin) (Hyclone, USA). Medium was changed every 3 days and cells reached total confluence after 5–6 days of initial seeding. For subculture, cells were dissociated with trypsin-ethylenediaminetetraacetic acid (Sigma-Aldrich, USA), split 1:3 and subcultured in  Petri dish More Detailses with 25 cm2 of growth area. Caco-2 cells were maintained in 5% of CO2, 95% of humidified atmosphere at 37°C.

Evaluation of cytotoxic activities

The cytotoxicity studies were adapted from the work developed by Pinteus et al.[11] Cells were seeded in 96-well plates and assays were done after cells reached the total confluence. Algae extracts were dissolved in culture medium without FBS and sterile filtered (0.2 μm Whatman, UK). Then, the cells were incubated 24 h with the extracts (1 mg/mL). For extracts that showed the highest activities, the effects were evaluated after 12 h of incubation, and they were also subjected to dose-response analysis (10–1000 μg/mL; 24 h).

Evaluation of antiproliferative activities

The antiproliferative studies were adapted from the work developed by Yuan and Walsh.[22] Cells were seeded in 96-well plates, and after 36 h of initial seeding, they were incubated 24 h with algae extracts (1 mg/mL), previously dissolved in MEM supplemented with FBS and sterile filtered (0.2 μm Whatman, UK). Extracts that produced effects at 24 h were also evaluated after 12 and 48 h of incubation and were subjected to dose-response analysis (10–1000 μg/mL; 24 h).

Evaluation of cytotoxic and antiproliferative effects of algae extracts on Caco-2 cells by 3- [4, 5-dimethylthiazol-2-yl]-2, 5-diphenyl tetrazolium bromide method

Cytotoxicity and cell proliferation tests were evaluated through the 3- [4, 5-dimethylthiazol-2-yl]-2, 5-diphenyl tetrazolium bromide (MTT) method. This assay is based on cleavage of tetrazolium salt MTT by mitochondrial dehydrogenase of viable cells to form a blue formazan product. The formazan produced is proportional to the number of living cells present and can be measured colorimetrically.[22] After the treatment with the methanolic and dichloromethane extracts, the medium was removed and cells were washed with Hank's buffer (composition, in mM: NaCl 137, KCl 5, MgSO4 0.8, Na2 HPO4 0.33, KH2 PO4 0.44, CaCl2 0.25; MgCl2 1.0, Tris HCl 0.15, and sodium butyrate 1.0, pH = 7.4). Cells were then incubated 4 h at 37°C with 1.2 mM MTT (Sigma-Aldrich, Germany) which was previously dissolved in Hank's buffer. The formazan products were dissolved in isopropanol (Panreac, Spain) containing 0.04 N HCl and quantified spectrophotometrically at 570 nm.

Evaluation of algae extracts effects on Caco-2 cell's viability and proliferation by the calcein-AM method

For the extracts that exhibited high activity through the MTT assay, it was used a fluorometric method to cross results, the calcein-AM (Invitrogen, USA) method. The membrane-permeant calcein-AM, a nonfluorescent dye, is taken up and converted by intracellular esterases to calcein, which in turn is not permeable and emits green fluorescence that can be quantified.[23] After treatment with algae extracts, cells were washed twice with Hank's buffer and loaded with 2 μM calcein-AM, previously prepared in the same buffer, and incubated at room temperature for 30 min. The natural fluorescence of cells was determined on previously defined wells, incubated with Hank's buffer without calcein-AM. Fluorescence was measured at 485 nm excitation and 530 nm emission wavelengths in a multiplate reader (Spectramax Gemini, Molecular Devices).

Data analysis

The results of both studies were expressed in percentage in relation to the control, calculated as:

(% of control) = (Abssample/Abscontrol)×100

One-way analysis of variance was used followed by Dunnett test to discriminate significant differences between algae extracts and controls (or vehicle). These analyzes were performed with GraphPad InStat for Windows (GraphPad Software, La Jolla, CA, USA). Results are presented as mean ± standard error of the mean. The significance level was inferred at P< 0.05 or P< 0.01 for all statistical tests.


   Results Top


Cytotoxicity induced by algae extracts on Caco-2 cells

The methanolic and dichloromethane extracts of 12 algae from Peniche coast, belonging to the Heterokontophyta, Rhodophyta, and Chlorophyta divisions, were tested on Caco-2 cells. Among the methanolic extracts (1 mg/mL; 24 h), the highest capacity to reduce Caco-2 cell's viability was exhibited by Asparagopsis armata (7.32% ±1.17% of viable cells), Sphaerococcus coronopifolius (3.53% ±1.26% of viable cells), and Fucus spiralis (23.68% ±2.93% of viable cells). The methanolic extracts of algae belonging to the Chlorophyta division (green algae) did not show any activity on Caco-2 cell's viability [Figure 1]a.
Figure 1: The effects on Caco-2 cell's viability induced by methanolic (a) and dichloromethane, (b) extracts of algae (1 mg/mL) (% of control) after 24 h obtained by 3-[4, 5-dimethylthiazol-2-yl]-2, 5-diphenyl tetrazolium bromide method. Each column represents the mean of eight experiments per group;vertical lines show standard error of the mean.#P < 0.01 and *P < 0.05 compared with control

Click here to view


Regarding results of dichloromethane extracts, it is possible to observe in [Figure 1]b that algae belonging to Rhodophyta division demonstrated the highest cytotoxic potential, namely, A. armata (1.04% ±0.39% of viable cells), Plocamium cartilagineum (9.77% ±2.28% of viable cells), and S. coronopifolius (1.92% ±0.89% of viable cells). The green alga Codium adhaerens also showed cytotoxic activity (83.97% ±1.40% of viable cells). For other side, dichloromethane extract of Heterokontophyta division did not exhibit any activity on Caco-2 cell's viability. For the extracts that exhibited capacity to reduce the cell's viability in at least 50%, we decided to corroborate the results using a fluorescence method (calcein-AM). The extracts were incubated with Caco-2 cells on the same conditions of the MTT method (1 mg/mL; 24 h). It is possible to verify that both extracts of A. armata (1.04% ±0.39% of viable cells) and S. coronopifolius presented the highest activity on Caco-2 cell's viability reduction [Figure 2], attesting therefore the previous results. For algae with major potential, we decided to understand if the effects were dependent of the concentration (10–1000 μg/mL; 24 h). The dichloromethane extract of S. coronopifolius displayed the smallest IC50 with 21.3 μg/mL (12.9–35.2). The results were summarized in [Table 2]. The next step was to comprehend if the effects induced on Caco-2 cell's viability were time dependent (12 and 24 h at 1 mg/mL). All extracts showed dependence of the time, excepting the dichloromethane extract of S. coronopifolius (0.33% ±0.18% of viable cells) that displayed a total reduction of cell viability after 12 h of incubation. This alga exhibited the highest potential in both extracts after 12 h [Figure 3].
Figure 2: The effects on Caco-2 cell's viability induced by methanolic and dichloromethane extracts of algae (1 mg/mL) (% of control) with highest activity (>50%) after 24 h obtained by calcein-AM method. Each column represents the mean of eight experiments per group; vertical lines show standard error of the mean. P < 0.01 compared with control

Click here to view
Figure 3: The effects on Caco-2 cell's viability induced by methanolic (a) and dichloromethane (b) extracts of algae (1 mg/mL) (% of control) with highest activity (>50%) after 12 h and 24 h obtained by 3-[4, 5-dimethylthiazol-2-yl]-2, 5-diphenyl tetrazolium bromide method. Each column represents the mean of eight experiments per group; vertical lines show standard error of the mean.#P < 0.01 compared with control

Click here to view
Table 2: IC50 values for the methanolic and dichloromethane extracts that showed the highest reduction of Caco-2 cell's viability (>50%) on maximum concentration (1000 μg/mL; 24 h)

Click here to view


Antiproliferative activity induced by algae extracts on Caco-2 cells

The antiproliferative activity of the different extracts obtained from 12 algae collected in Peniche coast (Portugal) was tested on Caco-2 cells. The cells were incubated with extracts at 1 mg/mL (24 h) after 36 h of the initial seeding. The results are shown in [Figure 4]. For both, extracts are possible to see that only the algae belonging to Rhodophyta and Heterokontophyta showed capacity to inhibit Caco-2 cell's proliferation. However, the major potential was exhibited by red algae (Rhodophyta) A. armata and S. coronopifolius methanolic extracts (24.32% ±7.56% of viable cells; 9.27% ±3.26% of viable cells, respectively) [Figure 4]a and dichloromethane extracts (0% ±0.48% of viable cells; 0.96% ±0.51% of viable cells, respectively) [Figure 4]b. The extracts that demonstrated capacity to inhibit the cell's proliferation in more than 50% were also screened through the calcein-AM method. The results showed a more marked effect on the inhibition of Caco-2 cell proliferation comparing with the results obtained by the MTT method. The dichloromethane extract of P. cartilagineum did not showed antiproliferative potential by this method [Figure 5]. For the extracts that exhibited high inhibition of Caco-2 cells, proliferation was evaluated the potency of the effects. The IC50 was defined testing different extract concentrations (10–1000 μg/mL) during 24 h. The results are represented in [Table 3] and showed that S. coronopifolius had the smallest IC50 both in the methanolic and dichloromethane extract, with 227.1 μg/mL (161.0–320.3) and 36.5 μg/mL (22.5–59.2), respectively. A. armata also demonstrated an interesting IC50 on the dichloromethane extract with an value of 271.5 μg/mL (165.5–445.4). The time-course effects were assessed for the extracts that displayed the highest inhibition of Caco-2 cell's proliferation (1 mg/mL; 24 h). In this assay, the extracts were tested at 12, 24 and 48 h at 1 mg/mL. The methanolic extract of A. armata showed dependence of the time between 12 and 24 h, maintaining the effects after 48 h. By other side, methanolic extract of S. coronopifolius displayed the same inhibition in all incubation times as well as the dichloromethane extract of A. armata. Dichloromethane fraction of S. coronopifolius showed similar inhibition at 12 h and 24 h but lost activity after 48 h. P. cartilagineum showed dependence between 12 and 24 h and maintained approximately the activity after 48 h [Figure 6]a and [Figure 6]b.
Figure 4: The effects induced on Caco-2 cell's proliferation by methanolic (a) and dichloromethane (b) extracts of algae (1 mg/mL) (% of control) after 24 h and dichloromethane extracts of algae (1 mg/mL) (% of control) with highest activity (>50%) after 24 h obtained by calcein-AM method. Each column represents the mean of eight experiments per group; vertical lines show standard error of the mean.#P < 0.01 compared with control

Click here to view
Figure 5: The effects induced on Caco-2 cell's proliferation by methanolic and dichloromethane extracts of algae (1 mg/mL) (% of control) with highest activity (>50%) after 24 h obtained by calcein-AM method. Each column represents the mean of eight experiments per group; vertical lines show standard error of the mean.#P < 0.01 compared with control

Click here to view
Figure 6: The effects induced on Caco-2 cell's proliferation by methanolic (a) and dichloromethane (b) extracts of algae (1 mg/mL) (% of control) with highest activity (>50%) after 12 h, 24 h, and 48 h obtained by 3-[4, 5-dimethylthiazol-2-yl]-2, 5-diphenyl tetrazolium bromide method. Each column represents the mean of eight experiments per group; vertical lines show standard error of the mean.#P < 0.01 compared with control

Click here to view
Table 3: IC50 values for the methanolic and dichloromethane extracts that showed highest inhibition of Caco-2 cell's proliferation (>50%) on maximum concentration (1000 μg/mL; 24 h)

Click here to view



   Discussion Top


The present study was designed to evaluate the antitumor activities of different algae collected from the Portugal coast (Peniche) on an in vitro model of human colorectal cancer. The data gathered here indicated that four algae (F. spiralis, A. armata, P. cartilagineum, and S. coronopifolius) have interesting potential. Cancer represents a major threat against human health and one of the major causes of death in humans. Therefore, there is an increasing interest on the search and development of new anticancer drugs from marine resources.[2],[24] The results obtained in this work are not surprising since algae are described as a rich source of structurally diverse secondary metabolites which includes terpenes, acetogenins, alkaloids, and polyphenolics, with many of these compounds being halogenated, which already reveal different biological activities.[25],[26] It was possible to verify a high decrease of Caco-2 cell's viability and proliferation induced by algae belonging to Heterokontophyta (brown algae) and Rhodophyta (red algae) phylum. These effects can be associated with the presence of SP, which in previous works showed antiproliferative activities. SP can be found in variable amounts in the three major divisions of marine algae, Rhodophyta, Heterokontophyta, and Chlorophyta.[27],[28],[29] Fucans, for example, were effective on several tumor cells, such as HL60 cells, sarcoma 180, murine colon cancer cell line (CT-26), mouse melanoma cell line (B-16), and human leukemia cell line (U-937).[30] As regards to F. spiralis, the activity exhibited can be mediated by the presence of fucoidan since this molecule was previously isolated from Fucus vesiculosus and strongly inhibited the growth of HCT-15 cells (human colon carcinoma cells).[31] In fact, polysaccharides are strong candidates to mediate the cytotoxic effects associated with F. spiralis since these molecules can be obtained with a methanolic extraction. Moreover, previous studies suggest that mechanisms mediated by fucoidan indicate induction of apoptotic processes in intestine tumor lines.[31],[32],[33] In line with these findings, this study also shows a possible cytotoxicity mechanism independent of the cell cycle inhibition since the cytotoxic effects were significantly more potent than the antiproliferative effects. However, more studies will be necessary to understand these mechanisms. Red algae (Rhodophyta division) produce a variety of secondary metabolites with considerable interest, such as mono and halogenated diterpenes, sterols, alkaloids, polyphenols, and sulfated sugars.[34] Some of these molecules have showed interesting antitumor activities on different cell lines, as for example the monoterpene-pentahalogenated halomon, which it was isolated from the red alga Portieria hornemannii and shown to have cytotoxic activity on several cancer cell lines, including colon cancer cell lines.[25],[35],[36] These potential could also be observed by the extracts of A. armata and S. coronopifolius. Several studies have reported the antimicrobial activity of A. armata on different types of microorganisms; however, as concerns to cytotoxicity screenings, there are few studies.[36],[37] Nevertheless, diterpenes with great interest were isolated from S. coronopifolius collected in the Mediterranean Sea. These molecules showed interesting results on different cellular lines and were able to overcome the natural resistance of certain tumor cells to apoptosis. Although the species studied in this work were collected from the Atlantic Coast, these molecules can also be responsible for the potent effect exhibited by the dichloromethane extract of S. coronopifolius.[38],[39],[40] The algae belonging to Chlorophyta did not showed activity on Caco-2 cells; however, previous studies reported antiproliferative activity by these kind of algae, namely, by SP isolated from Ulva lactuca that inhibit human epithelial colorectal adenocarcinoma cell's (Caco-2) proliferation.[30],[41] For other side, the Codium fragile specimen studied by Villarreal-Gómez et al. (2010) did not show activity on HCT-116 cells (colorectal cancer). This situation may seem divergent; nevertheless, diverse authors have described that the bioactivities are strongly related with temporal-space variations. Moreover, the toxicity varies even intraspecies and interspecies, depending on the community or the season, pointing to the important role of biotic and abiotic factors in the production of chemical defenses by these organisms.[14],[42],[43] These facts can explain the data obtained for green species in this study. Regarding the time-dependent proliferation studies, all extracts showed time-dependent effects between 12 and 24 h. Nevertheless, the dichloromethane extract of P. cartilagineum and S. coronopifolius lost activity after 48 h of incubation. This fact can be explained by the existence of tumor cells that have capacity to recover from the toxicity induced by the dichloromethane extract. Analyzing the potency of the effects, the smallest IC50 was exhibited by the dichloromethane extract of S. coronopifolius in cytotoxicity and antiproliferative tests, with 21.3 and 36.5 μg/mL, respectively. These results are particularly interesting when comparing with the IC50 obtained for cisplatin (commercial drug) in cytotoxicity and antiproliferative tests (80.02 and 91.08 μg/mL, respectively), in the same test conditions of the algae extracts. It is possible to verify that the values obtained by dichloromethane extract of these algae are substantially lower.


   Conclusion Top


Our results indicate that the extracts of A. armata, F. spiralis, P. cartilagineum, and S. coronopifolius may contain compounds with great antitumor potential. Therefore, these algae reveal to be promising sources for new molecules with application on cancer therapeutics. However, it is very important to isolate and purify the molecules responsible for these activities and define their mechanisms of action, for instance through analysis of cell cycle impacts, the ability to activate caspases, and through the analysis of mitochondrial and DNA damages.

Financial support and sponsorship

This study had the support of the Fundação para a Ciência e a Tecnologia (FCT) through Red2Discovery Project (PTDC/MAR-BIO/6149/2014), co-financed by COMPETE (POCI-01-0145-FEDER-016791), and Strategic Project UID/MAR/04292/2013 granted to MARE and the support of the FP7 EU project “BAMMBO: Sustainable Production of Biologically Active Molecules of Marine Based Origin” (FP7 n 265896/http//www.bammbo.eu). C.A, S.P. and A.H. are financially supported by a grant from FCT - Fundação para a Ciência e Tecnologia (SFRH/BD/97764/2013, SFRH/BD/96203/2013 and SFRH/BD/120250/2016, respectively).

Conflicts of interest

There are no conflicts of interest.



 
   References Top

1.
Rodrigues D, Alves C, Horta A, Pinteus S, Silva J, Culioli G, et al. Antitumor and antimicrobial potential of bromoditerpenes isolated from the red alga, Sphaerococcus coronopifolius. Mar Drugs 2015;13:713-26.  Back to cited text no. 1
[PUBMED]    
2.
Senn HJ, Otto F. Clinical Cancer Prevention. Heidelberg: Springer; 2011.  Back to cited text no. 2
    
3.
Society AC. Cancer Facts & Figures 2017. Atlanta: American Cancer Society; 2017.  Back to cited text no. 3
    
4.
Minev B. Cancer Management in Man: Chemotherapy, Biological Therapy, Hyperthermia and Supporting Measures. Heidelberg: Springer; 2011.  Back to cited text no. 4
    
5.
Haefner B. Drugs from the deep: Marine natural products as drug candidates. Drug Discov Today 2003;8:536-44.  Back to cited text no. 5
[PUBMED]    
6.
Murray PM, Moane S, Collins C, Beletskaya T, Thomas OP, Duarte AW, et al. Sustainable production of biologically active molecules of marine based origin. N Biotechnol 2013;30:839-50.  Back to cited text no. 6
[PUBMED]    
7.
Horta A, Alves C, Pinteus S, Pedrosa R. The marine origin of drugs. In: Botana LM, Alfonso A, editors. Phycotoxins, Chemistry and Biochemistry. 2nd ed. Chichester: John Wiley and Sons, Ltd.; 2015. p. 293-316.  Back to cited text no. 7
    
8.
Kijjoa A, Sawangwong P. Drugs and cosmetics from the sea. Mar Drugs 2004;2:73-82.  Back to cited text no. 8
    
9.
Plouguerné E, Ioannou E, Georgantea P, Vagias C, Roussis V, Hellio C, et al. Anti-microfouling activity of lipidic metabolites from the invasive brown alga Sargassum muticum (Yendo) Fensholt. Mar Biotechnol (NY) 2010;12:52-61.  Back to cited text no. 9
    
10.
Shalaby EA. Algae as promising organisms for environment and health. Plant Signal Behav 2011;6:1338-50.  Back to cited text no. 10
[PUBMED]    
11.
Pinteus S, Silva J, Alves C, Horta A, Fino N, Rodrigues AI, et al. Cytoprotective effect of seaweeds with high antioxidant activity from the Peniche coast (Portugal). Food Chem 2017;218:591-9.  Back to cited text no. 11
[PUBMED]    
12.
Pinteus S, Alves C, Monteiro H, Araújo E, Horta A, Pedrosa R. Asparagopsis armata and Sphaerococcus coronopifolius as a natural source of antimicrobial compounds. World J Microbiol Biotechnol 2015;31:445-51.  Back to cited text no. 12
    
13.
Zubia M, Fabre MS, Kerjean V, Lann KL, Stiger-Pouvreau V, Fauchon M, et al. Antioxidant and antitumoural activities of some Phaeophyta from Brittany coasts. Food Chem 2009;116:693-701.  Back to cited text no. 13
    
14.
Taskin E, Caki Z, Ozturk M. Assessment of in vitro antitumoral and antimicrobial activities of marine algae harvested from the Eastern Mediterranean sea. Afr J Biotechnol 2010;9:4272-7.  Back to cited text no. 14
    
15.
Kelman D, Posner EK, McDermid KJ, Tabandera NK, Wright PR, Wright AD. Antioxidant activity of Hawaiian marine algae. Mar Drugs 2012;10:403-16.  Back to cited text no. 15
    
16.
Lins KO, Bezerra DP, Alves AP, Alencar NM, Lima MW, Torres VM, et al. Antitumor properties of a sulfated polysaccharide from the red seaweed Champia feldmannii (Diaz-Pifferer). J Appl Toxicol 2009;29:20-6.  Back to cited text no. 16
    
17.
Nakazawa Y, Sashima T, Hosokawa M, Miyashita K. Comparative evaluation of growth inhibitory effect of stereoisomers of fucoxanthin in human cancer cell lines. J Funct Foods 2009;1:88-97.  Back to cited text no. 17
    
18.
Thoppil RJ, Bishayee A. Terpenoids as potential chemopreventive and therapeutic agents in liver cancer. World J Hepatol 2011;3:228-49.  Back to cited text no. 18
    
19.
Stabili L, Acquaviva MI, Biandolino F, Cavallo RA, De Pascali SA, Fanizzi FP, et al. The lipidic extract of the seaweed Gracilariopsis longissima (Rhodophyta, Gracilariales): A potential resource for biotechnological purposes? N Biotechnol 2012;29:443-50.  Back to cited text no. 19
    
20.
Araújo R, Barbara I, Tibaldo M, Berecibar E, Tapia P, Pereira R, et al. Checklist of benthic marine algae and Cyanobacteria of Northern Portugal. Bot Mar 2009;52:24-46.  Back to cited text no. 20
    
21.
Berecibar E, Wynne M, Barbara I, Santos S. Records of Rhodophyta new to the flora of the Iberian Atlantic coast. Bot Mar 2009;52:217-28.  Back to cited text no. 21
    
22.
Yuan YV, Walsh NA. Antioxidant and antiproliferative activities of extracts from a variety of edible seaweeds. Food Chem Toxicol 2006;44:1144-50.  Back to cited text no. 22
    
23.
Pedrosa R, Soares-da-Silva P. Oxidative and non-oxidative mechanisms of neuronal cell death and apoptosis by L-3,4-dihydroxyphenylalanine (L-DOPA) and dopamine. Br J Pharmacol 2002;137:1305-13.  Back to cited text no. 23
    
24.
Sithranga Boopathy N, Kathiresan K. Anticancer drugs from marine flora: An overview. J Oncol 2010;2010:214186.  Back to cited text no. 24
    
25.
de Almeida CL, Falcão Hde S, Lima GR, Montenegro Cde A, Lira NS, de Athayde-Filho PF, et al. Bioactivities from marine algae of the genus Gracilaria. Int J Mol Sci 2011;12:4550-73.  Back to cited text no. 25
    
26.
Kuo YH, Liang TW, Liu KC, Hsu YW, Hsu HC, Wang SL. Isolation and identification of a novel antioxidant with antitumour activity from Serratia ureilytica using squid pen as fermentation substrate. Mar Biotechnol (NY) 2011;13:451-61.  Back to cited text no. 26
    
27.
Shanmugam M, Mody K. Heparinoid-active sulphated polysaccharides from marine algae as potential blood anticoagulant agents. Curr Sci 2000;79:1672-83.  Back to cited text no. 27
    
28.
Silva TH, Alves A, Popa EG, Reys LL, Gomes ME, Sousa RA, et al. Marine algae sulfated polysaccharides for tissue engineering and drug delivery approaches. Biomatter 2012;2:278-89.  Back to cited text no. 28
    
29.
Skriptsova AV, Shevchenko NM, Tarbeeva DV, Zvyagintseva TN. Comparative study of polysaccharides from reproductive and sterile tissues of five brown seaweeds. Mar Biotechnol (NY) 2012;14:304-11.  Back to cited text no. 29
    
30.
Costa LS, Fidelis GP, Cordeiro SL, Oliveira RM, Sabry DA, Câmara RB, et al. Biological activities of sulfated polysaccharides from tropical seaweeds. Biomed Pharmacother 2010;64:21-8.  Back to cited text no. 30
    
31.
Hyun JH, Kim SC, Kang JI, Kim MK, Boo HJ, Kwon JM, et al. Apoptosis inducing activity of fucoidan in HCT-15 colon carcinoma cells. Biol Pharm Bull 2009;32:1760-4.  Back to cited text no. 31
    
32.
Imbs TI, Krasovskaya NP, Ermakova SP, Makarieva TN, Shevchenko NM, Zvyagintseva TN. Comparative study of chemical composition and antitumor activity of aqueous-ethanol extracts of brown algae Laminaria cichorioides, Costaria costata, and Fucus evanescens. Russ J Mar Biol 2009;35:164-70.  Back to cited text no. 32
    
33.
Ale MT, Maruyama H, Tamauchi H, Mikkelsen JD, Meyer AS. Fucoidan from Sargassum sp. and Fucus vesiculosus reduces cell viability of lung carcinoma and melanoma cells in vitro and activates natural killer cells in mice in vivo. Int J Biol Macromol 2011;49:331-6.  Back to cited text no. 33
    
34.
Allmendinger A, Spavieri J, Kaiser M, Casey R, Hingley-Wilson S, Lalvani A, et al. Antiprotozoal, antimycobacterial and cytotoxic potential of twenty-three British and Irish red algae. Phytother Res 2010;24:1099-103.  Back to cited text no. 34
    
35.
Jha R, Zi-Rong X. Biomedical compounds from marine organisms. Mar Drugs 2004;2:123-46.  Back to cited text no. 35
    
36.
Zubia M, Fabre MS, Kerjean V, Deslandes E. Antioxidant and cytotoxic activities of some red algae (Rhodophyta) from Brittany coasts (France). Bot Mar 2009;52:268-77.  Back to cited text no. 36
    
37.
Alves C, Pinteus S, Horta A, Pedrosa R. High cytotoxicity and anti-proliferative activity of algae extracts on an in vitro model of human hepatocellular carcinoma. Springerplus 2016;5:1339.  Back to cited text no. 37
    
38.
Smyrniotopoulos V, Quesada A, Vagias C, Moreau D, Roussakis C, Roussis V. Cytotoxic bromoditerpenes from the red alga Sphaerococcus coronopifolius. Tetrahedron 2008;64:5184-90.  Back to cited text no. 38
    
39.
Smyrniotopoulos V, Vagias C, Bruyère C, Lamoral-Theys D, Kiss R, Roussis V. Structure and in vitro antitumor activity evaluation of brominated diterpenes from the red alga Sphaerococcus coronopifolius. Bioorg Med Chem 2010;18:1321-30.  Back to cited text no. 39
    
40.
Piazza V, Roussis V, Garaventa F, Greco G, Smyrniotopoulos V, Vagias C, et al. Terpenes from the red alga Sphaerococcus coronopifolius inhibit the settlement of barnacles. Mar Biotechnol (NY) 2011;13:764-72.  Back to cited text no. 40
    
41.
Cavas L, Baskin Y, Yurdakoc K, Olgun N. Antiproliferative and newly attributed apoptotic activities from an invasive marine alga: Caulerpa racemosa var. cylindracea. J Exp Mar Biol Ecol 2006;339:111-9.  Back to cited text no. 41
    
42.
Marti R, Uriz M, Turon X. Seasonal and spatial variation of species toxicity in Mediterranean seaweed communities: Correlation to biotic and abiotic factors. Mar Ecol Prog Ser 2004;282:73-85.  Back to cited text no. 42
    
43.
Osman M, Abushady A, Elshobary M. In vitro screening of antimicrobial activity of extracts of some macroalgae collected from Abu-Qir bay Alexandria, Egypt. Afr J Biotechnol 2010;9:7203-8.  Back to cited text no. 43
    


    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6]
 
 
    Tables

  [Table 1], [Table 2], [Table 3]



 

Top
  
 
  Search
 
    Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
    Access Statistics
    Email Alert *
    Add to My List *
* Registration required (free)  

 
  In this article
    Abstract
   Introduction
    Materials and Me...
   Results
   Discussion
   Conclusion
    References
    Article Figures
    Article Tables

 Article Access Statistics
    Viewed1567    
    Printed78    
    Emailed0    
    PDF Downloaded42    
    Comments [Add]    

Recommend this journal