Abstract
In screening for novel photosensitizers for photodynamic therapy, 14 seaweed samples from Port Dickson in Malaysia were collected. Methanolic extracts of these samples were prepared and evaluated for phototoxicity using a short-term cell viability assay, where promyelocytic leukemia cells, HL60 were incubated with the extracts prior to irradiation with a broad spectrum light at 9.6 J cm−2 (equivalent to 10.5 mW cm−2 for 10 min). Four of the methanolic extracts demonstrated moderate to strong phototoxicity and bioassay-guided isolation of photosensitizers was carried out on two selected seaweeds to yield a total of eight cyclic tetrapyrrolic compounds which are derivatives of chlorophyll-a and -b. Seven of these compounds showed >50% phototoxicity at 5 μg mL−1 while exhibiting minimal cytotoxicity in the dark, which is an important characteristic of an ideal photosensitizer.
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References
Blunt JW, Copp BR, Munro MHG, Northcote PT, Prinsep MR (2011) Marine natural products. Nat Prod Rep 28:196–268
Chan CX, Ho CL, Phang SM (2006) Trends in seaweed research. Trends Plant Sci 11:165–166
Chee CF, Lee HB, Ong HC, Ho ASH (2005) Photocytotoxic pheophorbide-related compounds from Aglaonema simplex. Chem Biodivers 2:1648–1655
Cheng HH, Wang HK, Ito J, Bastow KF, Tachibana Y, Nakanishi Y, Xu Z, Luo TY, Lee KH (2001) Cytotoxic Pheophorbide-related compounds from Clerodendrum calamitosum and C. cyrtophyllum. J. Nat. Prod.: 915–919
Chopin T, Sawhney M (2009) Seaweeds and their mariculture. In: Steele JH, Thorpe SA, Turekian KK (eds) The encyclopedia of ocean sciences. Elsevier, Oxford, pp 4477–4487
Di Stefano A, Ettorre A, Sbrana S, Giovani C, Neri P (2001) Purpurin-18 in combination with light leads to apoptosis or necrosis in HL60 leukemia cells. Photochem Photobiol 73:290–296
Garido JL, Zapata M (2006) Chlorophyll cnalysis by new high performance liquid chromatography methods. In: Grimm B, Porra RJ, Rüdiger W, Scheer H (eds) Chlorophylls and bacteriochlorophylls: biochemistry, biophysics, functions and applications. Springer, The Netherlands, pp 109–119
Hoober JK, Sery TW, Yamatomo N (1988) Photodynamic sensitizers from chlorophyll: purpurin-18 and chlorin p6. Photochem Photobiol 48:579–582
Hörtensteiner S (1999) Chlorophyll breakdown in higher plants and algae. Cell Mol Life Sci 56:330–347
Jeffrey SW (1976) The occurrence of chlorophyll c1 and c2 in algae. J Phycol 12:349–354
Kamal N, Sabaratnam V, Abdullah N, Ho ASH, Teo SH, Lee HB (2009) Light-activated cytotoxic compounds from Malaysian microorganisms for photodynamic therapy of cancer. Antonie Van Leeuwenhoek 95:179–188
Kessel D, Smith K (1989) Photosensitization with derivatives of chlorophyll. Photochem Photobiol 49:157–160
Kim KK, Kawano Y, Yamazaki Y (2003) A novel porphyrin photosensitizer from bamboo leaves that induces apoptosis in cancer cell lines. Anticancer Res 23:2355–2361
Kobayashi M, Akiyama M, Kano H, Kise H (2006) Spectroscopy and structure determination. In: Grimm B, Porra RJ, Rüdiger W, Scheer H (eds) Chlorophylls and bacteriochlorophylls: biochemistry, biophysics, functions and applications. Springer, The Netherlands, pp 79–94
Larkum AWD, Kühl M (2005) Chlorophyll d: the puzzle resolved. Trends Plant Sci 10:355–357
Lim SH, Nowak-Sliwinska P, Kamarulzaman FA, Van Den Bergh H, Lee HB (2010) The neovessel occlusion efficacy of 151-hydroxypurpurin-7-Lactone dimethyl ester induced with photodynamic therapy. Photochem Photobiol 86:397–402
Ma L, Dolphin D (1996) Stereoselective synthesis of new chlorophyll a related antioxidants isolated from marine organisms. J Org Chem 61:2501–2510
Macdonald IJ, Dougherty TJ (2001) Basic principles of photodynamic therapy. J Porphyr Phthalocyanines 5:105–129
Mayer AMS, Gustafson KR (2006) Marine pharmacology in 2003–2004: anti-tumour and cytotoxic compounds. Eur J Cancer 42:2241–2270
Mironov A, Efremov A, Efremova O, Bonnett R (1997) Novel chlorins with δ-lactone ring. Mendeleevsk Commun 7:244–245
Miyashita H, Ikemoto H, Kurano N, Adachi K, Chihara M, Miyachi S (1996) Chlorophyll d as a major pigment. Nature 383:402
Murakami A, Miyashita H, Iseki M, Adachi K, Mimuro M (2004) Chlorophyll d in an epiphytic cyanobacterium of red algae. Science 303:1
Naylor CC, Keely BJ (1998) Sedimentary purpurins: oxidative transformation products of Chlorophylls. Org Geochem 28:417–422
Nyman ES, Hynninen PH (2004) Research advances in the use of tetrapyrrolic photosensitizers for photodynamic therapy. J Photochem Photobiol B Biol 73:1–28
Ocampo R, Repeta DJ (1999) Structural determination of purpurin-18 (as methyl ester) from sedimentary organic matter. Org Geochem 30:189–193
Ohta S, Ono F, Shiomi Y, Nakao T, Aozasa O, Nagate T, Kitamura K, Yamaguchi S, Nishi M, Miyata H (1998) Anti-Herpes Simplex Virus substances produced by the marine green alga, Dunaliella primolecta. J Appl Phycol 10:349–355
Ong CY, Ling SK, Ali RM, Chee CF, Samah ZA, Ho ASH, Teo SH, Lee HB (2009) Systematic analysis of in vitro photo-cytotoxic activity in extracts from terrestrial plants in Peninsula Malaysia for photodynamic therapy. J Photochem Photobiol B Biol 96:216–222
Pandey R, Bellnier D, Smith K, Dougherty T (1991) Chlorin and porphyrin derivatives as potential photosensitizers in photodynamic therapy. Photochem Photobiol 53:65–72
Pervaiz S (2001) Reactive oxygen-dependent production of novel photochemotherapeutic agents. FASEB J 15:612–617
Phang SM (2006) Seaweed resources in Malaysia: current status and future prospects. Aquat Ecosyst Health Manag 9:185–202
Rho MC, Chung MY, Song HY, Kwon OE, Lee SW, Baek JA, Jeune KH, Kim K, Lee HS, Kim YK (2003) Pheophorbide a-methyl ester, Acyl-CoA: cholesterol acyltransferase inhibitor from Diospyros kaki. Arch Pharm Res 26:716–718
Simmons TL, Andrianasolo E, McPhail K, Flatt P, Gerwick WH (2005) Marine natural products as anticancer drugs. Mol Cancer Ther 4:333–342
Sreenivasan S, Ibrahim D, Mohd Kassim MJN (2007) Free radical scavenging activity and total phenolic compounds of Gracilaria changii. Int J Nat Eng Sci 1:115–117
Vairappan CS (2003) Potent antibacterial activity of halogenated metabolites from Malaysian red algae, Laurencia majuscula (Rhodomelaceae, Ceramiales). Biomol Eng 20:255–259
Vairappan CS, Goh PN, Ang MY (2007) Antibacterial activity of fine chemicals from Scenedesmus acuminatus (Scenedesmaceae, Chlorococcales, Chlorophyta). Malays J Sci 26:65–72
Wongsinkongman P, Brossi A, Wang HK, Bastow KF, Lee KH (2002) Antitumor agents. Part 209: Pheophorbide-a derivatives as photo-Independent cytotoxic agents. Bioorg Med Chem 10:583–591
Zheng G, Aoudia M, Lee D, Rodgers MA, Smith KM, Dougherty TJ, Pandey RK (2000) Chlorin-based symmetrical and unsymmetrical dimers with amide linkages: effect of the substituents on photodynamic and photophysical properties. J Chem Soc Perkin Trans 1:3113–3121
Acknowledgments
The authors are grateful to the sponsors of Cancer Research Initiatives Foundation (CARIF) for supporting this work and the collaborators for their assistance in taxonomic identification and NMR experiments. The first author thanks the University of Malaya for the research grant (Vot PPP No. PS104/2007B; PS175/2008A) in support of this work.
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Tang, Y.V., Phang, S.M., Chu, W.L. et al. Cyclic tetrapyrrolic photosensitizers from Cladophora patentiramea (Cladophoraceae, Chlorophyta) and Turbinaria conoides (Sargassaceae, Phaeophyta) for photodynamic therapy. J Appl Phycol 24, 783–790 (2012). https://doi.org/10.1007/s10811-011-9698-8
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DOI: https://doi.org/10.1007/s10811-011-9698-8