Abstract
Tumor invasion and immortality are the most unfavorable drawbacks after cancer treatment. In this study, we focus on determining the photodynamic modulation of the proteolytic enzymes, matrix metalloproteinases (MMP); and a core catalytic subunit of telomerase, the human telomerase reverse transcriptase (hTERT) in medulloblastoma (MED) cell line (TE-671). Hexvix (ALA-H) mediated photodynamic therapy (PDT) demonstrated greater efficacy than 5-aminolevulinic acid (5-ALA) in terms of drug uptake and anti-proliferative effect. Both MMP-2 and hTERT expression are down-regulated quantitatively using ELISA and reverse-transcriptase-PCR (RT-PCR) respectively at post-treatment for this cell line. The MMP-9 expression remains unchanged after treatment. Further, there is a statistically significant inhibition of cell migration at 24 h post-ALA-H-PDT at LD50 (0.01 mM, 2 J cm-2; p < 0.001) in MED TE-671 cells. Evidently, MMP-2 and hTERT mRNA expressions can be the targets for the photodynamic intervention on tumor cell migration and immortality. Hence,PDT may be an alternate cancer regime for medulloblastoma.
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D. S. Russell and L. J. Rubinstein, Pathology of tumours of the nervous system, Williams & Wilkins, Baltimore, 5th, 1989, pp. 83–448.
S. Marino, Medulloblastoma: developmental mechanisms out of control, Trends Mol. Med., 2005, 11, 17–22.
New Cases Registered of Childhood and Adolescent Cancer in 2003, Hong Kong Cancer Registry, Hong Kong Hospital Authority
H. T. Whelan, H. G. Krouwer, M. H. Schmidt, K. W. Reichert, E. H. Kovnar, Current therapy and new perspectives in the treatment of medulloblastoma, Pediatr. Neurol., 1998, 18, 103–115.
M. Chintagumpala, S. Berg, S. M. Blaney, Treatment controversies in medulloblastoma, Curr. Opin. Oncol., 2001, 13, 154–159.
C. H. Sibata, V. C. Colussi, N. L. Oleinick, T. J. Kinsella, Photodynamic therapy in oncology, Expert Opin. Pharmacother., 2001, 2, 917–927.
H. Fukuda, A. Casas, A. Batlle, Aminolevulinic acid: from its unique biological function to its star role in photodynamic therapy, Int. J. Biochem. Cell Biol., 2005, 37, 272–276.
C. M. N. Yow, N. K. Mak, S. Szeto, J. Y. Chen, Y. L. Lee, N. H. Cheung, D. P. Huang, A. W. N. Leung, Photocytotoxic and DNA damaging effect of temoporfin (mTHPC) and merocyanine 540 (MC540) on nasopharygeal carcinoma cell, Toxicol. Lett., 2000, 115, 53–61.
W. N. Leung, X. Sun, N. K. Mak, C. M. N. Yow, Photodynamic effects of mTHPC on human colon adenocarcinoma cells: photocytotoxicity, subcellular localization and apoptosis, Photochem. Photobiol., 2002, 75, 406–411.
F. Rancan, A. Wiehe, M. Nobel, M. O. Senge, S. A. Omari, F. Bohm, M. John, B. Roder, Influence of substitutions on asymmetric dihydroxychlorins with regard to intracellular uptake, subcellular localization and photosensitization of Jurkat cells, J. Photochem. Photobiol., B, 2005, 78, 17–28.
P. J. Lou, L. Jones, C. Hooper, Clinical outcomes of photodynamic therapy for head-and-neck cancer, Technol. Cancer Res. Treat., 2003, 2, 311–317.
H. Kato, M. Harada, S. Ichinose, J. Usuda, T. Tsuchida, T. Okunaka, Photodynamic therapy (PDT) of lung cancer: experience of the Tokyo Medical University, Photodiagn. Photodyn. Ther., 2004, 1, 49–55.
S. S. Stylli, M. Howes, L. MacGregor, P. Rajendra, A. H. Kaye, Photodynamic therapy of brain tumors: evaluation of porphyrin uptake versus clinical outcome, J. Clin. Neurosci., 2004, 11, 584–596.
L. Ayaru, S. G. Bown, S. P. Pereira, Photodynamic therapy for pancreatic and biliary tract carcinoma, Int. J. Gastrointest. Cancer, 2005, 35, 1–14.
Z. Kachra, E. Beaulieu, L. Delbecchi, N. Mousseau, F. Berthelet, R. Moumdjian, R. Del. Maestro, R. Beliveau, Expression of matrix metalloproteinases and their inhibitors in human brain tumors, Clin. Exp. Metastas., 1999, 17, 555–566.
D. Ribatti, G. Surico, A. Vacca, F. De Leonardis, G. Lastilla, P. G. Montaldo, N. Rigillo, M. Ponzoni, Angiogenesis extent and expression of matrix metalloproteinase-2 and -9 correlate with progression in human neuroblastoma, Life Sci., 2001, 68, 1161–1168.
A. F. Chambers, L. M. Matrisian, Changing views of the role of matrix metalloproteinases in metastasis, J. Natl. Cancer Inst., 1997, 89, 1260–1270.
X. Xu, Y. Wang, Z. Chen, M. D. Sternlicht, M. Hidalgo, B. Steffensen, Matrix metalloproteinase-2 contributes to cancer cell migration on collagen, Cancer Res., 2005, 65, 130–136.
B. Davidson, I. Goldberg, W. H. Gotlieb, J. Kopolovic, G. Ben-Baruch, J. M. Nesland, A. Berner, M. Bryne, R. Reich, High levels of MMP-2, MMP-9, MT1-MMP and TIMP-2 mRNA correlate with poor survival in ovarian carcinoma, Clin. Exp. Metastas., 1999, 17, 799–808.
T. Yoneda, A. Sasaki, C. Dunstan, P. J. Williams, F. Bauss, Y. A. De Clerck, G. R. Mundy, Inhibition of osteolytic bone metastasis of breast cancer by combined treatment with the bisphosphonate ibandronate and tissue inhibitor of the matrix metalloproteinase-2, J. Clin. Invest., 1997, 99, 2509–2517.
N. W. Kim, M. A. Piatyszek, K. R. Prowse, C. B. Harley, M. D. West, P. L. Ho, G. M. Coviello, W. E. Wright, S. L. Weinrich, J. W. Shay, Specific association of human telomerase activity with immortal cells and cancer, Science, 1994, 266, 2011–2015.
M. N. Helder, G. B. A. Wisman, A. G. J. van der Zee, Telomerase and telomeres: from basic biology to cancer treatment, Cancer Invest., 2002, 20, 82–101.
Y. S. Cong, W. E. Wright, J. W. Shay, Human telomerase and its regulation, Microbiol. Mol. Biol. Rev., 2002, 66, 407–425.
W. Yasui, H. Tahara, E. Tahara, J. Fujimoto, J. Nakayama, F. Ishikawa, T. Ide, E. Tahara, Expression of telomerase catalytic component, telomerase reverse transcriptase, in human gastric carcinomas, Jpn. J. Cancer Res., 1998, 89, 1099–1103.
K. Ohuchida, K. Mizumoto, Y. Ogura, N. Ishikawa, E. Nagai, K. Yamaguchi, M. Tanaka, Quantitative assessment of telomerase activity and human telomerase reverse transcriptase messenger RNA levels in pancreatic juice samples for the diagnosis of pancreatic cancer, Clin. Cancer Res., 2005, 11, 2285–2292.
Y. Li, L. Li, T. J. Brown, P. Heldin, Silencing of hyaluronan synthase 2 suppresses the malignant phenotype of invasive breast cancer cells, Int. J. Cancer, 2007, 120, 2557–2567.
L. Liu, L. Han, D. Y. Wong, P. Y. Yue, W. Y. Ha, Y. H. Hu, P. X. Wang, R. N. Wong, Effects of Si-Jun-Zi decoction polysaccharides on cell migration and gene expression in wounded rat intestinal epithelial cells, Br. J. Nutr., 2005, 93, 21–29.
P. Jichlinski, H. J. Leisinger, Photodynamic therapy in superficial bladder cancer: past, present and future, Urol. Res., 2001, 29, 396–405.
C. M. N. Yow, J. Y. Chen, N. K. Mak, N. H. Cheung, A. W. N. Leung, Cellular uptake, subcellular localization and photodamaging effect of temoporfin (mTHPC) in nasopharyngeal carcinoma cells: comparison with hematoporphyrin derivative (HPD), Cancer Lett., 2000, 157, 123–131.
C. M. Au, S. K. Luk, C. J. Jackson, H. K. Ng, C. M. N. Yow, T. S. S. To, Differential effects of photofrin, 5-aminolevulinic acid and calphostin C on glioma cells, J. Photochem. Photobiol., B, 2006, 85, 92–101.
A. Juzeniene, P. Juzenas, V. Iani, J. Moan, Topical application of 5-aminolevulinic acid and its methylester, hexylester and octylester derivatives: considerations for dosimetry in mouse skin model, Photochem. Photobiol., 2002, 76, 329–34.
S. L. Gibson, M. L. Nguyen, J. J. Havens, A. Barbarin, R. Hilf, Relationship of delta-aminolevulinic acid-induced protoporphyrin IX levels to mitochondrial content in neoplastic cells in vitro, Biochem. Biophys. Res. Commun., 1999, 265, 315–321.
H. Brunner, F. Hausmann, R. C. Krieg, E. Endlicher, J. Scholmerich, R. Knuechel, H. Messmann, The effects of 5-aminolevulinic acid esters on protoprophyrin IX production in human adenocarcinoma cell lines, Photochem. Photobiol., 2001, 74, 617–623.
R. F. Turchiello, F. C. Vena, P. Maillard, C. S. Souza, M. V. Bentley, A. C. Tedesco, Cubic phase gel as a drug delivery system for topical application of 5-ALA, its ester derivatives and m-THPC in photodynamic therapy (PDT), J. Photochem. Photobiol., B, 2003, 70, 1–6.
E. S. M. Chu, R. W. K. Wu, C. M. N. Yow, T. K. S. Wong, J. Y. Chen, The cytotoxic and genotoxic potential of 5-aminolevulinic acid on lymphocytes: a comet assay study, Cancer Chemother. Pharmacol., 2006, 58, 408–414.
R. W. K. Wu, E. S. M. Chu, C. M. N. Yow, J. Y. Chen, Photodynamic effects on nasopharyngeal carcinoma (NPC) cells with 5-aminolevulinic acid or its hexyl ester, Cancer Lett., 2006, 242, 112–119.
P. G. Fisher, P. C. Burger, C. G. Eberhart, Biological risk stratification of Medulloblastoma: the real time is now, J. Clin. Oncol., 2004, 22, 971–974.
H. K. Rooprai, D. McCormick, Proteinases and their inhibitors in human brain tumours: a review, Anticancer Res., 1997, 17, 4151–4162.
M. D. Sternlicht, Z. Werb, How matrix metalloproteinases regulate cell behaviour, Annu. Rev. Cell Dev. Biol., 2001, 17, 463–516.
M. Nakada, D. Kita, K. Futami, J. Yamashita, N. Fujimoto, H. Sato, Y. Okada, Roles of membrane type 1 matrix metalloproteinase and tissue inhibitor of metalloproteinases-2 in invasion and dissemination of human malignant glioma, J. Neurosurg., 2001, 94, 464–473.
S. Curran, G. I. Murray, Matrix metalloproteinases in tumor invasion and metastasis, J. Pathol., 1999, 189, 300–308.
G. H. Vince, C. Herbold, R. Klein, J. Kuhl, T. Pietsch, S. Franz, K. Roosen, J. C. Tonn, Medulloblastoma displays distinct regional matrix metalloprotease expression, J. Neuro-Oncol., 2001, 53, 99–106.
O. Ozen, B. Krebs, B. Hemmerlein, A. Pekrun, H. Kretzschmar, J. Herms, Expression of matrix metalloproteinases and their inhibitors in medulloblastomas and their prognostic relevance, Clin. Cancer Res., 2004, 10, 4746–4753.
P. A. Forsyth, H. Wong, T. D. Laing, N. B. Rewcastle, D. G. Morris, H. Muzik, K. J. Leco, R. N. Johnston, P. M. A. Brasher, G. Sutherland, D. R. Edward, Gelatinase-A (MMP-2), gelatinase-B (MMP-9) and membrane type matrix metalloproteinase-1 (MT-MMP) are involved in different aspects of the pathophysiology of malignant gliomas, Br. J. Cancer, 1999, 79, 1828–1835.
S. Karrer, A. K. Bosserhoff, P. Weiderer, M. Landthaler, R. M. Szeimies, Keratinocyte-derived cytokines after photodynamic therapy and their paracrine induction of matrix metalloproteinases in fibroblasts, Br. J. Dermatol., 2004, 151, 776–783.
H. Takahashi, S. Komatsu, M. Ibe, A. Ishida-Yamamoto, S. Nakajima, I. Sakata, H. Iizuka, ATX-S10(Na)-PDT shows more potent effect on collagen metabolism of human normal and scleroderma dermal fibroblasts than ALA-PDT, Arch. Dermatol. Res., 2006, 298, 257–263.
C. M. N. Yow, E. S. M. Chu, T. K. S. Wong, Photodynamic therapy (PDT)-regulation of human telomerase: reverse transcriptase (hTERT) and matrix metalloproteinase (MMP-2) in human cancer cells, Proc. Am. Assoc. Cancer Res., 2005, 46, 283.
L. Hayflick, P. S. Moorhead, The serial cultivation of human diploid cell strains, Exp. Cell Res., 1961, 25, 585–621.
C. P. Chiu, C. B. Harley, Replicative senescence and cell immortality: the role of telomeres and telomerase, Proc. Soc. Exp. Biol. Med., 1997, 214, 99–106.
V. Urquidi, D. Tarin, S. Goodison, Role of telomerase in cell senescence and oncogenesis, Annu. Rev. Med., 2000, 51, 65–79.
A. Schindler, U. Fiedler, A. Meye, U. Schmidt, S. Fussel, C. Pilarsky, J. Herrmann, M. P. Wirth, Human telomerase reverse transcriptase antisense treatment down-regulates the viability of prostate cancer cells in vitro, Int. J. Oncol., 2001, 19, 25–30.
M. M. Leon-Blanco, J. M. Guerrero, R. J. Reiter, D. Pozo, RNA expression of human telomerase subunits TR and TERT is differentially affected by melatonin receptor agonists in the MCF-7 tumor cell line, Cancer Lett., 2004, 216, 73–80.
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Chu, E.S.M., Wong, T.K.S. & Yow, C.M.N. Photodynamic effect in medulloblastoma: downregulation of matrix metalloproteinases and human telomerase reverse transcriptase expressions. Photochem Photobiol Sci 7, 76–83 (2008). https://doi.org/10.1039/b703417b
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DOI: https://doi.org/10.1039/b703417b