Share This Article:

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

Full-Text HTML XML Download Download as PDF (Size:1168KB) PP. 98-108
DOI: 10.4236/abc.2014.42014    3,960 Downloads   6,153 Views   Citations

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 alterations 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.

Conflicts of Interest

The authors declare no conflicts of interest.

Cite this paper

Gambato, G. , Baroni, É. , Garcia, C. , Frassini, R. , Frozza, C. , Moura, S. , Pereira, C. , Fujii, M. , Colepicolo, P. , Lambert, A. , Henriques, J. and Roesch-Ely, M. (2014) Brown Algae Himantothallus grandifolius (Desmarestiales, Phaeophyceae) Suppresses Proliferation and Promotes Apoptosis-Mediated Cell Death in Tumor Cells. Advances in Biological Chemistry, 4, 98-108. doi: 10.4236/abc.2014.42014.

References

[1] Glaser, K.B. and Mayer, A.M. (2009) A Renaissance in Marine Pharmacology: From Preclinical Curiosity to Clinical Reality. Biochemical Pharmacology, 78, 440-448.
http://dx.doi.org/10.1016/j.bcp.2009.04.015
[2] Iken, K., Amsler, C.D., Hubbard, J.M., McClintock, J.B. and Baker, B.J. (2007) Allocation Patterns of Phlorotannins in Antarctic Brown Algae. Phycologia, 46, 386-395.
http://dx.doi.org/10.2216/06-67.1
[3] Grahan, L.E., Grahan, J.M. and Wilcox, L.W. (2009) Algae. 616 p.
[4] Gressler, V., Yokoya, N.S., Fujii, M.T., Colepicolo, P., Mancini Filho, J. and Torres, R.P. (2010) Lipid, Fatty Acid, Protein, Amino Acid and Ash Contents in Four Brazilian Red Algae Species. Food Chemistry, 120, 585-590.
http://dx.doi.org/10.1016/j.foodchem.2009.10.028
[5] Gressler, V., Fujii, M.T., Martins, A.P., Colepicolo, P., Mancini-Filho, J. and Pinto, E. (2011) Biochemical Composition of Two Red Seaweed Species Grown on the Brazilian Coast. Journal of the Science of Food and Agriculture, 91, 1687-1692.
http://dx.doi.org/10.1002/jsfa.4370
[6] McConnaughey, E. (1985) Sea Vegetables, Harvesting Guide & Cookbook. 239 p.
[7] Ichimura, M., Kato, S., Tsuneyama, K., Matsutake, S., Kamogawa, M., Hirao, E., Miyata, A., Mori, S., Yamaguchi, N., Suruga, K., et al. (2013) Phycocyanin Prevents Hypertension and Low Serum Adiponectin Level in a Rat Model of Metabolic Syndrome. Nutrition Research, 33, 397-405.
http://dx.doi.org/10.1016/j.nutres.2013.03.006
[8] Park, Y.K., Rasmussen, H.E., Ehlers, S.J., Blobaum, K.R., Lu, F., Schlegal, V.L., Carr, T.P. and Lee, J.Y. (2008) Repression of Proinflammatory Gene Expression by Lipid Extract of Nostoc Commune var Sphaeroides Kutzing, a Blue-Green Alga, via Inhibition of Nuclear Factor-Kappab in RAW 264.7 Macrophages. Nutrition Research, 28, 83-91.
http://dx.doi.org/10.1016/j.nutres.2007.11.008
[9] Pereira, H., Barreira, L., Figueiredo, F., Custodio, L., Vizetto-Duarte, C., Polo, C., Resek, E., Engelen, A. and Varela, J. (2012) Polyunsaturated Fatty Acids of Marine Macroalgae: Potential for Nutritional and Pharmaceutical Applications. Marine Drugs, 10, 1920-1935.
http://dx.doi.org/10.3390/md10091920
[10] Chan, Y.., Kim, K.H. and Cheah, S.H. (2011) Inhibitory Effects of Sargassum Polycystum on Tyrosinase Activity and Melanin Formation in B16F10 Murine Melanoma Cells. Journal of Ethnopharmacology, 137, 1183-1188.
http://dx.doi.org/10.1016/j.jep.2011.07.050
[11] Liu, L., Heinrich, M., Myers, S. and Dworjanyn, S.A. (2012) Towards a Better Understanding of Medicinal Uses of the Brown Seaweed Sargassum in Traditional Chinese Medicine: A Phytochemical and Pharmacological Review. Journal of Ethnopharmacology, 142, 591-619.
http://dx.doi.org/10.1016/j.jep.2012.05.046
[12] Quartino, M.L., Zaixso, H.E. and Boraso de Zaixso, A.L. (2005) Biological and Environmental Characterization of Marine Macroalgal Assemblages in Potter Cove, South Shetland Islands, Antarctica. Botanica Marina, 48, 187-197.
http://dx.doi.org/10.1515/BOT.2005.029
[13] Quartino, M.L., Deregibus, D., Campana, G.L., Latorre, G.E. and Momo, F.R. (2013) Evidence of Macroalgal Colonization on Newly Ice-Free Areas Following Glacial Retreat in Potter Cove (South Shetland Islands), Antarctica. PLoS One, 8, e58223.
http://dx.doi.org/10.1371/journal.pone.0058223
[14] Park, E.J. and Pezzuto, J.M. (2013) Antioxidant Marine Products in Cancer Chemoprevention. Antioxid Redox Signal, 19, 115-138.
http://dx.doi.org/10.1089/ars.2013.5235
[15] Yotsu-Yamashita, M., Kondo, S., Segawa, S., Lin, Y.C., Toyohara, H., Ito, H., Konoki, K., Cho, Y. and Uchida, T. (2013) Isolation and Structural Determination of Two Novel Phlorotannins from the Brown Alga Ecklonia Kurome Okamura, and Their Radical Scavenging Activities. Marine Drugs, 11, 165-183.
http://dx.doi.org/10.3390/md11010165
[16] Zhang, Z., Teruya, K., Yoshida, T., Eto, H. and Shirahata, S. (2013) Fucoidan Extract Enhances the Anti-Cancer Activity of Chemotherapeutic Agents in MDA-MB-231 and MCF-7 Breast Cancer Cells. Marine Drugs, 11, 81-98.
http://dx.doi.org/10.3390/md11010081
[17] Cardozo, K.H., Carvalho, V.M., Pinto, E. and Colepicolo, P. (2006) Fragmentation of Mycosporine-Like Amino Acids by Hydrogen/Deuterium Exchange and Electrospray Ionisation Tandem Mass Spectrometry. Rapid Communications in Mass Spectrometry, 20, 253-258.
http://dx.doi.org/10.1002/rcm.2305
[18] Lacorte, S. and Fernandez-Alba, A.R. (2006) Time of Flight Mass Spectrometry Applied to the Liquid Chromatographic Analysis of Pesticides in Water and Food. Mass Spectrometry Reviews, 25, 866-880.
http://dx.doi.org/10.1002/mas.20094
[19] El-Rafie, H.M., El-Rafie, M.H. and Zahran, M.K. (2013) Green Synthesis of Silver Nanoparticles Using Polysaccharides Extracted from Marine Macro Algae. Carbohydrate Polymers, 96, 403-410.
http://dx.doi.org/10.1016/j.carbpol.2013.03.071
[20] Berteau, O. and Mulloy, B. (2003) Sulfated Fucans, Fresh Perspectives: Structures, Functions, and Biological Properties of Sulfated Fucans and an Overview of Enzymes Active toward This Class of Polysaccharide. Glycobiology, 13, 29R-40R.
http://dx.doi.org/10.1093/glycob/cwg058
[21] Onofrejova, L., Vasickova, J., Klejdus, B., Stratil, P., Misurcova, L., Kracmar, S., Kopecky, J. and Vacek, J. (2010) Bioactive Phenols in Algae: The Application of Pressurized-Liquid and solid-Phase Extraction Techniques. Journal of Pharmaceutical and Biomedical Analysis, 51, 464-470.
http://dx.doi.org/10.1016/j.jpba.2009.03.027
[22] WHO (2013) World Health Organization (Internet).
http://www.who.int/en/
[23] Reichert, J.M. and Wenger, J.B. (2008) Development Trends for New Cancer Therapeutics and Vaccines. Drug Discovery Today, 13, 30-37.
http://dx.doi.org/10.1016/j.drudis.2007.09.003
[24] Skrovankova, S. (2011) Seaweed Vitamins as Nutraceuticals. Advances in Food and Nutrition Research, 64, 357-369.
http://dx.doi.org/10.1016/B978-0-12-387669-0.00028-4
[25] Khanavi, M., Nabavi, M., Sadati, N., Shams Ardekani, M., Sohrabipour, J., Nabavi, S.M., Ghaeli, P. and Ostad, S.N. (2010) Cytotoxic Activity of Some Marine Brown Algae against Cancer Cell Lines. Biological Research, 43, 31-37.
http://dx.doi.org/10.4067/S0716-97602010000100005
[26] Yeh, C.C., Yang, J.I., Lee, J.C., Tseng, C.N., Chan, Y.C., Hseu, Y.C., Tang, J.Y., Chuang, L.Y., Huang, H.W., Chang, F.R., et al. (2012) Anti-Proliferative Effect of Methanolic Extract of Gracilaria tenuistipitata on Oral Cancer Cells Involves Apoptosis, DNA Damage, and Oxidative Stress. BMC Complementary and Alternative Medicine, 12, 142.
http://dx.doi.org/10.1186/1472-6882-12-142
[27] Ryu, M.J., Kim, A.D., Kang, K.A., Chung, H.S., Kim, H.S., Suh, I.S., Chang, W.Y. and Hyun, J.W. (2013) The Green algae Ulva fasciata Delile Extract Induces Apoptotic Cell Death in Human Colon Cancer Cells. In Vitro Cellular & Developmental Biology-Animal, 49, 74-81.
http://dx.doi.org/10.1007/s11626-012-9547-3
[28] Li, Y., Qian, Z.J., Ryu, B., Lee, S.H., Kim, M.M. and Kim, S.K. (2009) Chemical Components and Its Antioxidant Properties in Vitro: An Edible Marine Brown Alga, Ecklonia cava. Bioorganic & Medicinal Chemistry, 17, 1963-1973.
http://dx.doi.org/10.1016/j.bmc.2009.01.031
[29] Yoon, J.S., Kasin Yadunandam, A., Kim, S.J., Woo, H.C., Kim, H.R., Kim, G.D. (2012) Dieckol, Isolated from Ecklonia stolonifera, Induces Apoptosis in Human Hepatocellular Carcinoma Hep3B Cells. Journal of Natural Medicines, 67, 519-527.
http://dx.doi.org/10.1007/s11418-012-0709-0
[30] Jin, U.H., Lee, J.Y., Kang, S.K., Kim, J.K., Park, W.H., Kim, J.G., Moon, S.K. and Kim, C.H. (2005) A Phenolic Compound, 5-Caffeoylquinic Acid (Chlorogenic Acid), Is a New Type and Strong Matrix Metalloproteinase-9 Inhibitor: Isolation and Identification from Methanol Extract of Euonymus alatus. Life Sciences, 77, 2760-2769.
http://dx.doi.org/10.1016/j.lfs.2005.02.028
[31] Belkaid, A., Currie, J.C., Desgagnes, J. and Annabi, B. (2006) The Chemopreventive Properties of Chlorogenic Acid Reveal a Potential New Role for the Microsomal Glucose-6-Phosphate Translocase in Brain Tumor Progression. Cancer Cell International, 6, 7.
http://dx.doi.org/10.1186/1475-2867-6-7
[32] Feng, R., Lu, Y., Bowman, L.L., Qian, Y., Castranova, V. and Ding, M. (2005) Inhibition of Activator Protein-1, NF-kappaB, and MAPKs and Induction of Phase 2 Detoxifying Enzyme Activity by Chlorogenic Acid. The Journal of Biological Chemistry, 280, 27888-27895.
http://dx.doi.org/10.1074/jbc.M503347200
[33] Kang, T.Y., Yang, H.R., Zhang, J., Li, D., Lin, J., Wang, L. and Xu, X. (2013) The Studies of Chlorogenic Acid Antitumor Mechanism by Gene Chip Detection: The Immune Pathway Gene Expression. Journal of Analytical Methods in Chemistry, 2013, Article ID: 617243.
http://dx.doi.org/10.1155/2013/617243
[34] Kerr, J.F., Wyllie, A.H. and Currie, A.R. (1972) Apoptosis: A Basic Biological Phenomenon with Wide-Ranging Implications in Tissue Kinetics. British Journal of Cancer, 26, 239-257.
http://dx.doi.org/10.1038/bjc.1972.33
[35] Ouyang, L., Shi, Z., Zhao, S., Wang, F.T., Zhou, T.T., Liu, B. and Bao, J.K. (2012) Programmed Cell Death Pathways in Cancer: A Review of Apoptosis, Autophagy and Programmed Necrosis. Cell Proliferation, 45, 487-498.
http://dx.doi.org/10.1111/j.1365-2184.2012.00845.x
[36] Sola, S., Morgado, A.L. and Rodrigues, C.M. (2013) Death Receptors and Mitochondria: Two Prime Triggers of Neural Apoptosis and Differentiation. Biochimica et Biophysica Acta, 1830, 2160-2166.
http://dx.doi.org/10.1016/j.bbagen.2012.09.021
[37] Kim, A.D., Lee, Y., Kang, S.H., Kim, G.Y., Kim, H.S. and Hyun, J.W. (2013) Cytotoxic Effect of Clerosterol Isolated from Codium Fragile on A2058 Human Melanoma Cells. Marine Drugs, 11, 418-430.
http://dx.doi.org/10.3390/md11020418
[38] Schutte, B., Nuydens, R., Geerts, H. and Ramaekers, F. (1998) Annexin V Binding Assay as a Tool to Measure Apoptosis in Differ-entiated Neuronal Cells. Journal of Neuroscience Methods, 86, 63-69.
http://dx.doi.org/10.1016/S0165-0270(98)00147-2
[39] van Engeland, M., Nieland, L.J., Ramaekers, F.C., Schutte, B. and Reutelingsperger, C.P. (1998) Annexin V-Affinity Assay: A Review on an Apoptosis Detection System Based on Phosphatidylserine Exposure. Cytometry, 31, 1-9.
http://dx.doi.org/10.1002/(SICI)1097-0320(19980101)31:1<1::AID-CYTO1>3.0.CO;2-R
[40] de la Mare, J.A., Lawson, J.C., Chiwakata, M.T., Beukes, D.R., Edkins, A.L. and Blatch, G.L. (2012) Quinones and Halogenated Monoterpenes of Algal Origin Show Anti-Proliferative Effects against Breast Cancer Cells in Vitro. Investigational New Drugs, 30, 2187-2200.
http://dx.doi.org/10.1007/s10637-011-9788-0
[41] Zhang, Z., Teruya, K., Eto, H. and Shirahata, S. (2013) Induction of Apoptosis by Low-Molecular-Weight Fucoidan through Calcium- and Caspase-Dependent Mitochondrial Pathways in MDA-MB-231 Breast Cancer Cells. Bioscience, Biotechnology, and Biochemistry, 77, 235-242.
[42] Hanahan, D. and Weinberg, R.A. (2011) Hallmarks of Cancer: The Next Generation. Cell, 144, 646-674.
http://dx.doi.org/10.1016/j.cell.2011.02.013
[43] Tan, M.L., Ooi, J.P., Ismail, N., Moad, A.I. and Muhammad, T.S. (2009) Programmed Cell Death Pathways and Current Antitumor Targets. Pharmaceutical Research, 26, 1547-1560.
http://dx.doi.org/10.1007/s11095-009-9895-1

  
comments powered by Disqus

Copyright © 2018 by authors and Scientific Research Publishing Inc.

Creative Commons License

This work and the related PDF file are licensed under a Creative Commons Attribution 4.0 International License.