Abstract
Photodynamic therapy (PDT) is a promising cancer treatment which involves activation of a photosensitizing drug with light to produce reactive oxygen species that kill tumors without causing damage to unirradiated normal tissues. To date, only Photofrin®, Foscan® and Levulan® have been approved for clinical treatment of cancer. Tropical habitats such as those found in Malaysia are attractive sources of new therapeutic compounds as tremendous chemical diversity is found in a large number of plants, animals, marine- and micro-organisms. In our screening program for novel photosensitizers from nature, colorful strains of fungi (from Aspergillus and Penicillium genus) and bacteria (including actinomycetes and photosynthetic bacteria) were collected from various habitats in Peninsular Malaysia, such as coastal soil, peat soil, marine sponges and wastewater ponds. Methanolic extracts from a total of 85 different species were evaluated with a short-term cell viability assay for photo-cytotoxicity, where a promyelocytic leukemia cell-line, HL60 incubated with 20 μg/ml of extracts was irradiated with 9.6 J/cm2 of a broad spectrum light. Two of these extracts, one from Rhodobacter sphaeroides (PBUM003) and one from Rhodopseudomonas palustris (PBUM001) showed moderate to strong photo-cytotoxicity. Subsequent bioassay guided isolation of the PBUM001 extract yielded known photosensitisers that are based on bacteriochlorophyll-a by comparing their molecular weight data, HPLC profiles and UV–vis absorption spectra with literature values, thereby demonstrating the validity of our screening approach.
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References
Allison RR, Downie GH, Cuenca R, Hu XH, Childs CJH, Sibata CH (2004) Photosensitizers in clinical PDT. Photodiagn Photodyn Ther 1:27–42. doi:10.1016/S1572-1000(04)00007-9
Annie Tan GY, Christabel L, Ho LS, Nik Zahirah NA, Sarini S, Vikineswary S (2005) Survey of culturable actinomycetes from marine macroorganisms and mangrove areas of Langkawi Islands. Malays J Sci 24:69–75
Beems EM, Dubbelman TM, Lugtenburg J, Van Best JA, Smeets MF, Boegheim JP (1987) Photosensitizing properties of bacteriochlorophyllin a and bacteriochlorin a, two derivatives of bacteriochlorophyll a. Photochem Photobiol 46:639–643. doi:10.1111/j.1751-1097.1987.tb04825.x
Boik J (2001) Natural compounds in cancer therapy. Oregon Medical Press, Minnesota, p 25
Bonett R (1989) A death ray of cancer. New Sci 28:56–58
Brandis A, Weiner L, Yahel VH, Pawlak A, Brumfeld V, Wilson BC, Mcllroy B, Scherz A, Rozanowska M, Sarna T, Salomon Y (2005) The microenvironment effect on the generation of reactive oxygen species by Pd-Bacteriopheophorbide. J Am Chem Soc 127:6487–6497. doi:10.1021/ja046210j
Brown JE, Brown SB, Vernon DI (1999) Photodynamic therapy—new light on cancer treatment. J Soc Dye Colour 115:249–253
Brun PH, Degroot JL, Gudgin Dickson EF, Farahani M, Pottier RH (2004) Neutron activation and liquid scintillation analysis of tissue samples containing palladium bacteriochlorophyll derivative, a potential photochemotherapeutic agent. Can J Anal Sci Spectrosc 49:55–63
Chen Y, Grahm A, Potter W, Morgan J, Vaughan L, Bellnier DA, Henderson BW, Oseroff A, Dougherty TJ, Pandey RK (2002) Bacteriopurpurinimides: highly stable and potent photosensitizers for photodynamic therapy. J Med Chem 45:255–258. doi:10.1021/jm010400c
Donadio S, Monciardini P, Alduina R, Mazza P, Chiocchini C, Cavaletti L, Sosio M, Puglia AM (2002) Microbial technologies for the discovery of novel bioactive metabolites. J Biotechnol 99:187–198. doi:10.1016/S0168-1656(02)00209-2
Getha K, Vikineswary S, Chong VC (1998) Isolation and growth of the phototrophic bacterium Rhodopseudomonas palustris strain PBUM001 in sago starch processing wastewater. World J Microbiol Biotechnol 14:505–511. doi:10.1023/A:1008855125634
Hasegawa T, Takizawa M, Tanida S (1983) A rapid analysis for chemical grouping of aerobic actinomycetes. J Gen Appl Microbiol 29:319–322. doi:10.2323/jgam.29.319
Ismet A, Parameswari S, Vikineswary S (2002) Diversity of Micromonospora in Malaysian mangrove rhizophere soil. Malays J Sci 21:51–59
Koudinova NV, Pinthus JH, Brandis A et al (2003) Photodynamic therapy with Pd-bacteriopheophorbide (TOOKAD): successful in vivo treatment of human prostatic small cell carcinoma xenografts. Int J Cancer 104(6):782–789. doi:10.1002/ijc.11002
Lee HB, Ho AS, Teo SH (2006) p53 status does not affect photodynamic cell killing induced by hypericin. Cancer Chemother Pharmacol 58:91–98. doi:10.1007/s00280-005-0131-3
Limantara L, Koehler P, Wilhelm B, Porra RJ, Scheer H (2006) Photostability of bacteriochlorophyll a and derivatives. Photochem Photobiol 82:770–780. doi:10.1562/2005-09-07-RA-676
Mosmann TJ (1983) Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods 65:55–63. doi:10.1016/0022-1759(83)90303-4
Pandey RK, Shiau F-Y, Sumlin AB, Dougherty TJ, Smith KM (1994) Syntheses of new bacteriochlorins and their antitumor activity. Bioorg Med Chem Lett 4:1263–1267. doi:10.1016/S0960-894X(01)80342-5
Scherz A, Salomon Y, Scheer H, Hartwich G, Brandis A (1996) Synthetic metal substituded bacteriochlorophyll derivatives and use thereof. US Patent, Application No. 09/077:208
Scherz A, Salomon Y, Scheer H, Brandis A (1999) Palladium-substituted bacteriochlorophyll derivatives and use thereof. International PCT Patent, Application No. PCT/ALB/00673
Shirling EB, Gottlieb D (1966) Methods for the characterization of Streptomyces species. Int J Syst Bacteriol 16:313–340
Sibata CH, Colussi VC, Oleinick NL, Kinsella TJ (2001) Photodynamic therapy in oncology. Expert Opin Pharmacother 2:917–927. doi:10.1517/14656566.2.6.917
Teuchner K, Stiel H, Leupold D, Scherz A, Noy D, Simonin I, Hartwich G, Scheer H (1997) Fluorescence and excited state absorption in modified pigments of bacterial photosynthesis a comparative study of metal-substituted bacteriochlorophylls a. J Lumin 72:612–614. doi:10.1016/S0022-2313(96)00411-5
Trachtenberg J, Bogaards A, Weersink RA, Haider MA, Evans A, McCluskey SA, Scherz A, Gertner MR, Yue C, Appu S, Aprikian A, Savard J, Wilson BC, Elhilali M (2007) Vascular targeted photodynamic therapy with palladium-bacteriopheophorbide photosensitizer for recurrent prostate cancer following definitive radiation therapy: assessment of safety and treatment response. J Urol 178:1974–1979. doi:10.1016/j.juro.2007.07.036
Van Niel CB (1931) On the morphology and physiology of the purple and green sulfur bacteria. Arch Microbiol 3:1–112. doi:10.1007/BF00454965
Weersink RA, Forbes J, Bisland S, Trachtenberg J, Elhilaili MM, Brun PH, Wilson BC (2005) Assessment of cutaneous photosensitivity of Tookad (WST09) in preclinical animal models and in patients. Photochem Photobiol 81:106–113. doi:10.1562/2004-05-31-RA-182.1
Zhenjun D, Lown LW (1990) Hypocrellins and their use in photosensitization. J Photochem Photobiol 52:609–616. doi:10.1111/j.1751-1097.1990.tb01807.x
Zilberstein J, Schreiber S, Bloemers MC, Bendel P, Neeman M, Schechtman E, Kohen F, Scherz A, Salomon Y (2001) Antivascular treatment of solid melanoma tumors with bacteriochlorophyll-serine-based photodynamic therapy. Photochem Photobiol 73:257–266. doi:10.1562/0031-8655(2001)073<0257:ATOSMT>2.0.CO;2
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We thank the sponsors of CARIF for supporting this work.
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Kamal, N., Sabaratnam, V., Abdullah, N. et al. Light-activated cytotoxic compounds from Malaysian microorganisms for photodynamic therapy of cancer. Antonie van Leeuwenhoek 95, 179–188 (2009). https://doi.org/10.1007/s10482-008-9301-8
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DOI: https://doi.org/10.1007/s10482-008-9301-8