Skip to main content
Top
Published in: Journal of Ovarian Research 1/2014

Open Access 01-12-2014 | Research

4-Methylumbelliferone inhibits ovarian cancer growth by suppressing thymidine phosphorylase expression

Authors: Ryosuke Tamura, Yoshihito Yokoyama, Hidemi Yoshida, Tadaatsu Imaizumi, Hideki Mizunuma

Published in: Journal of Ovarian Research | Issue 1/2014

Login to get access

Abstract

Background

4-Methylumbelliferone (4-MU), a hyaluronan (HA) synthesis inhibitor, has antitumor activity in cancer cells. However, few studies have focused on its effects on ovarian cancer. The aim of this study was to investigate the effects of 4-MU on ovarian cancer and to elucidate its mechanism of action.

Methods

The HRA human ovarian serous adenocarcinoma cell line was used in this study. The effects of 4-MU on cell proliferation, migration, and invasion were determined by using in vitro assays as well as an in vivo rat peritoneal carcinomatosis model. The expression of HA synthase (HAS), CD44 HA receptor, vascular endothelial growth factor (VEGF), and thymidine phosphorylase (TP) mRNA in HRA cells was analyzed by quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR).

Results

4-MU administration inhibited the growth of peritoneal tumors and significantly prolonged survival. In vitro experiments showed that 4-MU inhibited HRA cell proliferation in a dose-dependent manner, while it did not affect HRA cell invasion and migration. 4-MU significantly decreased TP mRNA expression in HRA cells. On the other hand, since HAS2, CD44, and VEGF endogenous mRNA expression levels were very low in HRA cells, it was impossible to evaluate the effect of 4-MU treatment.

Conclusions

These results suggest that 4-MU exerts its antitumor effect on ovarian cancer through suppressing TP expression.
Appendix
Available only for authorised users
Literature
1.
go back to reference Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D: Global cancer statistics. CA Cancer J Clin 2011,61(2):69–90. 10.3322/caac.20107CrossRefPubMed Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D: Global cancer statistics. CA Cancer J Clin 2011,61(2):69–90. 10.3322/caac.20107CrossRefPubMed
2.
go back to reference Ozols RF, Bundy BN, Greer BE, Fowler JM, Clarke-Pearson D, Burger RA, Mannel RS, DeGeest K, Hartenbach EM, Baergen R: Phase III trial of carboplatin and paclitaxel compared with cisplatin and paclitaxel in patients with optimally resected stage III ovarian cancer: a gynecologic oncology group study. J Clin Oncol 2003,21(17):3194–3200. 10.1200/JCO.2003.02.153CrossRefPubMed Ozols RF, Bundy BN, Greer BE, Fowler JM, Clarke-Pearson D, Burger RA, Mannel RS, DeGeest K, Hartenbach EM, Baergen R: Phase III trial of carboplatin and paclitaxel compared with cisplatin and paclitaxel in patients with optimally resected stage III ovarian cancer: a gynecologic oncology group study. J Clin Oncol 2003,21(17):3194–3200. 10.1200/JCO.2003.02.153CrossRefPubMed
3.
go back to reference Burger RA, Brady MF, Bookman MA, Fleming GF, Monk BJ, Huang H, Mannel RS, Homesley HD, Fowler J, Greer BE, Boente M, Birrer MJ, Liang SX: Incorporation of bevacizumab in the primary treatment of ovarian cancer. N Engl J Med 2011,365(26):2473–2483. 10.1056/NEJMoa1104390CrossRefPubMed Burger RA, Brady MF, Bookman MA, Fleming GF, Monk BJ, Huang H, Mannel RS, Homesley HD, Fowler J, Greer BE, Boente M, Birrer MJ, Liang SX: Incorporation of bevacizumab in the primary treatment of ovarian cancer. N Engl J Med 2011,365(26):2473–2483. 10.1056/NEJMoa1104390CrossRefPubMed
4.
go back to reference Ledermann J, Harter P, Gourley C, Friedlander M, Vergote I, Rustin G, Scott C, Meier W, Shapira-Frommer R, Safra T, Matei D, Macpherson E, Watkins C, Carmichael J, Matulonis U: Olaparib maintenance therapy in platinum-sensitive relapsed ovarian cancer. N Engl J Med 2012,366(15):1382–1392. 10.1056/NEJMoa1105535CrossRefPubMed Ledermann J, Harter P, Gourley C, Friedlander M, Vergote I, Rustin G, Scott C, Meier W, Shapira-Frommer R, Safra T, Matei D, Macpherson E, Watkins C, Carmichael J, Matulonis U: Olaparib maintenance therapy in platinum-sensitive relapsed ovarian cancer. N Engl J Med 2012,366(15):1382–1392. 10.1056/NEJMoa1105535CrossRefPubMed
5.
go back to reference Armstrong DK, White AJ, Weil SC, Phillips M, Coleman RL: Farletuzumab (a monoclonal antibody against folate receptor alpha) in relapsed platinum-sensitive ovarian cancer. Gynecol Oncol 2013,129(3):452–458. 10.1016/j.ygyno.2013.03.002CrossRefPubMed Armstrong DK, White AJ, Weil SC, Phillips M, Coleman RL: Farletuzumab (a monoclonal antibody against folate receptor alpha) in relapsed platinum-sensitive ovarian cancer. Gynecol Oncol 2013,129(3):452–458. 10.1016/j.ygyno.2013.03.002CrossRefPubMed
6.
go back to reference Monk BJ, Herzog TJ, Kaye SB, Krasner CN, Vermorken JB, Muggia FM, Pujade-Lauraine E, Lisyanskaya AS, Makhson AN, Rolski J, Gorbounova VA, Ghatage P, Bidzinski M, Shen K, Ngan HY, Vergote IB, Nam JH, Park YC, Lebedinsky CA, Poveda AM: Trabectedin plus pegylated liposomal doxorubicin in recurrent ovarian cancer. J Clin Oncol 2010,28(19):3107–3114. 10.1200/JCO.2009.25.4037CrossRefPubMed Monk BJ, Herzog TJ, Kaye SB, Krasner CN, Vermorken JB, Muggia FM, Pujade-Lauraine E, Lisyanskaya AS, Makhson AN, Rolski J, Gorbounova VA, Ghatage P, Bidzinski M, Shen K, Ngan HY, Vergote IB, Nam JH, Park YC, Lebedinsky CA, Poveda AM: Trabectedin plus pegylated liposomal doxorubicin in recurrent ovarian cancer. J Clin Oncol 2010,28(19):3107–3114. 10.1200/JCO.2009.25.4037CrossRefPubMed
7.
go back to reference Kakizaki I, Kojima K, Takagaki K, Endo M, Kannagi R, Ito M, Maruo Y, Sato H, Yasuda T, Mita S, Kimata K, Itano N: A novel mechanism for the inhibition of hyaluronan biosynthesis by 4-methylumbelliferone. J Biol Chem 2004,279(32):33281–33289. 10.1074/jbc.M405918200CrossRefPubMed Kakizaki I, Kojima K, Takagaki K, Endo M, Kannagi R, Ito M, Maruo Y, Sato H, Yasuda T, Mita S, Kimata K, Itano N: A novel mechanism for the inhibition of hyaluronan biosynthesis by 4-methylumbelliferone. J Biol Chem 2004,279(32):33281–33289. 10.1074/jbc.M405918200CrossRefPubMed
8.
go back to reference Miyake K, Underhill CB, Lesley J, Kincade PW: Hyaluronate can function as a cell adhesion molecule and CD44 participates in hyaluronate recognition. J Exp Med 1990,172(1):69–75. 10.1084/jem.172.1.69CrossRefPubMed Miyake K, Underhill CB, Lesley J, Kincade PW: Hyaluronate can function as a cell adhesion molecule and CD44 participates in hyaluronate recognition. J Exp Med 1990,172(1):69–75. 10.1084/jem.172.1.69CrossRefPubMed
9.
go back to reference Bourguignon LY, Spevak CC, Wong G, Xia W, Gilad E: Hyaluronan-CD44 interaction with protein kinase C (epsilon) promotes oncogenic signaling by the stem cell marker Nanog and the Production of microRNA-21, leading to down-regulation of the tumor suppressor protein PDCD4, anti-apoptosis, and chemotherapy resistance in breast tumor cells. J Biol Chem 2009,284(39):26533–26546. 10.1074/jbc.M109.027466PubMedCentralCrossRefPubMed Bourguignon LY, Spevak CC, Wong G, Xia W, Gilad E: Hyaluronan-CD44 interaction with protein kinase C (epsilon) promotes oncogenic signaling by the stem cell marker Nanog and the Production of microRNA-21, leading to down-regulation of the tumor suppressor protein PDCD4, anti-apoptosis, and chemotherapy resistance in breast tumor cells. J Biol Chem 2009,284(39):26533–26546. 10.1074/jbc.M109.027466PubMedCentralCrossRefPubMed
10.
go back to reference Bourguignon LY, Wong G, Earle C, Chen L: Hyaluronan-CD44v3 interaction with Oct4-Sox2-Nanog promotes miR-302 expression leading to self-renewal, clonal formation, and cisplatin resistance in cancer stem cells from head and neck squamous cell carcinoma. J Biol Chem 2012,287(39):32800–32824. 10.1074/jbc.M111.308528PubMedCentralCrossRefPubMed Bourguignon LY, Wong G, Earle C, Chen L: Hyaluronan-CD44v3 interaction with Oct4-Sox2-Nanog promotes miR-302 expression leading to self-renewal, clonal formation, and cisplatin resistance in cancer stem cells from head and neck squamous cell carcinoma. J Biol Chem 2012,287(39):32800–32824. 10.1074/jbc.M111.308528PubMedCentralCrossRefPubMed
11.
go back to reference Hiraga T, Ito S, Nakamura H: Cancer stem-like cell marker CD44 promotes bone metastases by enhancing tumorigenicity, cell motility, and hyaluronan production. Cancer Res 2013,73(13):4112–4122. 10.1158/0008-5472.CAN-12-3801CrossRefPubMed Hiraga T, Ito S, Nakamura H: Cancer stem-like cell marker CD44 promotes bone metastases by enhancing tumorigenicity, cell motility, and hyaluronan production. Cancer Res 2013,73(13):4112–4122. 10.1158/0008-5472.CAN-12-3801CrossRefPubMed
12.
go back to reference Kultti A, Pasonen-Seppänen S, Jauhiainen M, Rilla KJ, Kärnä R, Pyäriä E, Tammi RH, Tammi MI: 4-Methylumbelliferone inhibits hyaluronan synthesis by depletion of cellular UDP-glucuronic acid and downregulation of hyaluronan synthase 2 and 3. Exp Cell Res 2009,315(11):1914–1923. 10.1016/j.yexcr.2009.03.002CrossRefPubMed Kultti A, Pasonen-Seppänen S, Jauhiainen M, Rilla KJ, Kärnä R, Pyäriä E, Tammi RH, Tammi MI: 4-Methylumbelliferone inhibits hyaluronan synthesis by depletion of cellular UDP-glucuronic acid and downregulation of hyaluronan synthase 2 and 3. Exp Cell Res 2009,315(11):1914–1923. 10.1016/j.yexcr.2009.03.002CrossRefPubMed
13.
go back to reference Lokeshwar VB, Lopez LE, Munoz D, Chi A, Shirodkar SP, Lokeshwar SD, Escudero DO, Dhir N, Altman N: Antitumor activity of hyaluronic acid synthesis inhibitor 4-methylumbelliferone in prostate cancer cells. Cancer Res 2010,70(7):2613–2623. 10.1158/0008-5472.CAN-09-3185PubMedCentralCrossRefPubMed Lokeshwar VB, Lopez LE, Munoz D, Chi A, Shirodkar SP, Lokeshwar SD, Escudero DO, Dhir N, Altman N: Antitumor activity of hyaluronic acid synthesis inhibitor 4-methylumbelliferone in prostate cancer cells. Cancer Res 2010,70(7):2613–2623. 10.1158/0008-5472.CAN-09-3185PubMedCentralCrossRefPubMed
14.
go back to reference Urakawa H, Nishida Y, Wasa J, Arai E, Zhuo L, Kimata K, Kozawa E, Futamura N, Ishiguro N: Inhibition of hyaluronan synthesis in breast cancer cells by 4-methylumbelliferone suppresses tumorigenicity in vitro and metastatic lesions of bone in vivo. Int J Cancer 2012,130(2):454–466. 10.1002/ijc.26014CrossRefPubMed Urakawa H, Nishida Y, Wasa J, Arai E, Zhuo L, Kimata K, Kozawa E, Futamura N, Ishiguro N: Inhibition of hyaluronan synthesis in breast cancer cells by 4-methylumbelliferone suppresses tumorigenicity in vitro and metastatic lesions of bone in vivo. Int J Cancer 2012,130(2):454–466. 10.1002/ijc.26014CrossRefPubMed
15.
go back to reference Piccioni F, Malvicini M, Garcia MG, Rodriguez A, Atorrasagasti C, Kippes N, Piedra Buena IT, Rizzo MM, Bayo J, Aquino J, Viola M, Passi A, Alaniz L, Mazzolini G: Antitumor effects of hyaluronic acid inhibitor 4-methylumbelliferone in an orthotopic hepatocellular carcinoma model in mice. Glycobiology 2012,22(3):400–410. 10.1093/glycob/cwr158CrossRefPubMed Piccioni F, Malvicini M, Garcia MG, Rodriguez A, Atorrasagasti C, Kippes N, Piedra Buena IT, Rizzo MM, Bayo J, Aquino J, Viola M, Passi A, Alaniz L, Mazzolini G: Antitumor effects of hyaluronic acid inhibitor 4-methylumbelliferone in an orthotopic hepatocellular carcinoma model in mice. Glycobiology 2012,22(3):400–410. 10.1093/glycob/cwr158CrossRefPubMed
16.
go back to reference Kikuchi Y, Kizawa I, Oomori K, Miyauchi M, Kita T, Sugita M, Tenjin Y, Kato K: Establishment of a human ovarian cancer cell line capable of forming ascites in nude mice and effects of tranexamic acid on cell proliferation and ascites formation. Cancer Res 1987,47(2):592–596.PubMed Kikuchi Y, Kizawa I, Oomori K, Miyauchi M, Kita T, Sugita M, Tenjin Y, Kato K: Establishment of a human ovarian cancer cell line capable of forming ascites in nude mice and effects of tranexamic acid on cell proliferation and ascites formation. Cancer Res 1987,47(2):592–596.PubMed
17.
go back to reference Yokoyama Y, Hirakawa H, Wang H, Mizunuma H: Is omentectomy mandatory in the operation for ovarian cancer? Eur J Obstet Gynecol Reprod Biol 2012,164(1):89–92. 10.1016/j.ejogrb.2012.05.020CrossRefPubMed Yokoyama Y, Hirakawa H, Wang H, Mizunuma H: Is omentectomy mandatory in the operation for ovarian cancer? Eur J Obstet Gynecol Reprod Biol 2012,164(1):89–92. 10.1016/j.ejogrb.2012.05.020CrossRefPubMed
18.
go back to reference Yoshida H, Meng P, Matsumiya T, Tanji K, Hayakari R, Xing F, Wang L, Tsuruga K, Tanaka H, Mimura J, Kosaka K, Itoh K, Takahashi I, Imaizumi T: Carnosic acid suppresses the production of amyloid-β 1–42 and 1–43 by inducing an α-secretase TACE/ADAM17 in U373MG human astrocytoma cells. Neurosci Res 2014, 79: 83–93. doi:10.1016/j.neures.2013.11.004 10.1016/j.neures.2013.11.004CrossRefPubMed Yoshida H, Meng P, Matsumiya T, Tanji K, Hayakari R, Xing F, Wang L, Tsuruga K, Tanaka H, Mimura J, Kosaka K, Itoh K, Takahashi I, Imaizumi T: Carnosic acid suppresses the production of amyloid-β 1–42 and 1–43 by inducing an α-secretase TACE/ADAM17 in U373MG human astrocytoma cells. Neurosci Res 2014, 79: 83–93. doi:10.1016/j.neures.2013.11.004 10.1016/j.neures.2013.11.004CrossRefPubMed
19.
go back to reference Yokoyama Y, Xin B, Shigeto T, Umemoto M, Kasai-Sakamoto A, Futagami M, Tsuchida S, Al-Mulla F, Mizunuma H: Clofibric acid, a peroxisome proliferator-activated receptor alpha ligand, inhibits growth of human ovarian cancer. Mol Cancer Ther 2007,6(4):1379–1386. 10.1158/1535-7163.MCT-06-0722CrossRefPubMed Yokoyama Y, Xin B, Shigeto T, Umemoto M, Kasai-Sakamoto A, Futagami M, Tsuchida S, Al-Mulla F, Mizunuma H: Clofibric acid, a peroxisome proliferator-activated receptor alpha ligand, inhibits growth of human ovarian cancer. Mol Cancer Ther 2007,6(4):1379–1386. 10.1158/1535-7163.MCT-06-0722CrossRefPubMed
20.
go back to reference Meng P, Yoshida H, Matsumiya T, Imaizumi T, Tanji K, Xing F, Hayakari R, Dempoya J, Tatsuta T, Aizawa-Yashiro T, Mimura J, Kosaka K, Itoh K, Satoh K: Carnosic acid suppresses the production of amyloid-β 1–42 by inducing the metalloprotease gene TACE/ADAM17 in SH-SY5Y human neuroblastoma cells. Neurosci Res 2013, 75: 94–102. doi:10.1016/j.neures.2012.11.007 10.1016/j.neures.2012.11.007CrossRefPubMed Meng P, Yoshida H, Matsumiya T, Imaizumi T, Tanji K, Xing F, Hayakari R, Dempoya J, Tatsuta T, Aizawa-Yashiro T, Mimura J, Kosaka K, Itoh K, Satoh K: Carnosic acid suppresses the production of amyloid-β 1–42 by inducing the metalloprotease gene TACE/ADAM17 in SH-SY5Y human neuroblastoma cells. Neurosci Res 2013, 75: 94–102. doi:10.1016/j.neures.2012.11.007 10.1016/j.neures.2012.11.007CrossRefPubMed
21.
go back to reference Yoshihara S, Kon A, Kudo D, Nakazawa H, Kakizaki I, Sasaki M, Endo M, Takagaki K: A hyaluronan synthase suppressor, 4-methylumbelliferone, inhibits liver metastasis of melanoma cells. FEBS Lett 2005,579(12):2722–2726. 10.1016/j.febslet.2005.03.079CrossRefPubMed Yoshihara S, Kon A, Kudo D, Nakazawa H, Kakizaki I, Sasaki M, Endo M, Takagaki K: A hyaluronan synthase suppressor, 4-methylumbelliferone, inhibits liver metastasis of melanoma cells. FEBS Lett 2005,579(12):2722–2726. 10.1016/j.febslet.2005.03.079CrossRefPubMed
22.
go back to reference Arai E, Nishida Y, Wasa J, Urakawa H, Zhuo L, Kimata K, Kozawa E, Futamura N, Ishiguro N: Inhibition of hyaluronan retention by 4-methylumbelliferone suppresses osteosarcoma cells in vitro and lung metastasis in vivo. Br J Cancer 2011,105(12):1839–1849. 10.1038/bjc.2011.459PubMedCentralCrossRefPubMed Arai E, Nishida Y, Wasa J, Urakawa H, Zhuo L, Kimata K, Kozawa E, Futamura N, Ishiguro N: Inhibition of hyaluronan retention by 4-methylumbelliferone suppresses osteosarcoma cells in vitro and lung metastasis in vivo. Br J Cancer 2011,105(12):1839–1849. 10.1038/bjc.2011.459PubMedCentralCrossRefPubMed
23.
go back to reference Day AJ, Prestwich GD: Hyaluronan-binding proteins: tying up the giant. J Biol Chem 2002,277(7):4585–4588. 10.1074/jbc.R100036200CrossRefPubMed Day AJ, Prestwich GD: Hyaluronan-binding proteins: tying up the giant. J Biol Chem 2002,277(7):4585–4588. 10.1074/jbc.R100036200CrossRefPubMed
24.
go back to reference Ponta H, Sherman L, Herrlich PA: CD44: from adhesion molecules to signalling regulators. Nat Rev Mol Cell Biol 2003,4(1):33–45. 10.1038/nrm1004CrossRefPubMed Ponta H, Sherman L, Herrlich PA: CD44: from adhesion molecules to signalling regulators. Nat Rev Mol Cell Biol 2003,4(1):33–45. 10.1038/nrm1004CrossRefPubMed
25.
go back to reference Nykopp TK, Rilla K, Sironen R, Tammi MI, Tammi RH, Hämäläinen K, Heikkinen AM, Komulainen M, Kosma VM, Anttila M: Expression of hyaluronan synthases (HAS1–3) and hyaluronidases (HYAL1–2) in serous ovarian carcinomas: inverse correlation between HYAL1 and hyaluronan content. BMC Cancer 2009, 9: 143. doi:10.1186/1471–2407–9-143 10.1186/1471-2407-9-143PubMedCentralCrossRefPubMed Nykopp TK, Rilla K, Sironen R, Tammi MI, Tammi RH, Hämäläinen K, Heikkinen AM, Komulainen M, Kosma VM, Anttila M: Expression of hyaluronan synthases (HAS1–3) and hyaluronidases (HYAL1–2) in serous ovarian carcinomas: inverse correlation between HYAL1 and hyaluronan content. BMC Cancer 2009, 9: 143. doi:10.1186/1471–2407–9-143 10.1186/1471-2407-9-143PubMedCentralCrossRefPubMed
26.
go back to reference Anttila MA, Tammi RH, Tammi MI, Syrjänen KJ, Saarikoski SV, Kosma VM: High levels of stromal hyaluronan predict poor disease outcome in epithelial ovarian cancer. Cancer Res 2000,60(1):150–155.PubMed Anttila MA, Tammi RH, Tammi MI, Syrjänen KJ, Saarikoski SV, Kosma VM: High levels of stromal hyaluronan predict poor disease outcome in epithelial ovarian cancer. Cancer Res 2000,60(1):150–155.PubMed
27.
go back to reference Sohara Y, Ishiguro N, Machida K, Kurata H, Thant AA, Senga T, Matsuda S, Kimata K, Iwata H, Hamaguchi M: Hyaluronan activates cell motility of v-Src-transformed cells via Ras-mitogen-activated protein kinase and phosphoinositide 3-kinase-Akt in a tumor-specific manner. Mol Biol Cell 2001,12(6):1859–1868. 10.1091/mbc.12.6.1859PubMedCentralCrossRefPubMed Sohara Y, Ishiguro N, Machida K, Kurata H, Thant AA, Senga T, Matsuda S, Kimata K, Iwata H, Hamaguchi M: Hyaluronan activates cell motility of v-Src-transformed cells via Ras-mitogen-activated protein kinase and phosphoinositide 3-kinase-Akt in a tumor-specific manner. Mol Biol Cell 2001,12(6):1859–1868. 10.1091/mbc.12.6.1859PubMedCentralCrossRefPubMed
28.
go back to reference Saito T, Tamura D, Nakamura T, Makita Y, Ariyama H, Komiyama K, Yoshihara T, Asano R: 4-methylumbelliferone leads to growth arrest and apoptosis in canine mammary tumor cells. Oncol Rep 2013,29(1):335–342.PubMed Saito T, Tamura D, Nakamura T, Makita Y, Ariyama H, Komiyama K, Yoshihara T, Asano R: 4-methylumbelliferone leads to growth arrest and apoptosis in canine mammary tumor cells. Oncol Rep 2013,29(1):335–342.PubMed
29.
go back to reference Yoneda J, Kuniyasu H, Crispens MA, Price JE, Bucana CD, Fidler IJ: Expression of angiogenesis-related genes and progression of human ovarian carcinomas in nude mice. J Natl Cancer Inst 1998,90(6):447–454. 10.1093/jnci/90.6.447CrossRefPubMed Yoneda J, Kuniyasu H, Crispens MA, Price JE, Bucana CD, Fidler IJ: Expression of angiogenesis-related genes and progression of human ovarian carcinomas in nude mice. J Natl Cancer Inst 1998,90(6):447–454. 10.1093/jnci/90.6.447CrossRefPubMed
30.
go back to reference Yokoyama Y, Charnock-Jones DS, Licence D, Yanaihara A, Hastings JM, Holland CM, Emoto M, Umemoto M, Sakamoto T, Sato S, Mizunuma H, Smith SK: Vascular endothelial growth factor-D is an independent prognostic factor in epithelial ovarian carcinoma. Br J Cancer 2003,88(2):237–244. 10.1038/sj.bjc.6600701PubMedCentralCrossRefPubMed Yokoyama Y, Charnock-Jones DS, Licence D, Yanaihara A, Hastings JM, Holland CM, Emoto M, Umemoto M, Sakamoto T, Sato S, Mizunuma H, Smith SK: Vascular endothelial growth factor-D is an independent prognostic factor in epithelial ovarian carcinoma. Br J Cancer 2003,88(2):237–244. 10.1038/sj.bjc.6600701PubMedCentralCrossRefPubMed
31.
go back to reference García-Vilas JA, Quesada AR, Medina MÁ: 4-methylumbelliferone inhibits angiogenesis in vitro and in vivo. J Agric Food Chem 2013,61(17):4063–4071. 10.1021/jf303062hCrossRefPubMed García-Vilas JA, Quesada AR, Medina MÁ: 4-methylumbelliferone inhibits angiogenesis in vitro and in vivo. J Agric Food Chem 2013,61(17):4063–4071. 10.1021/jf303062hCrossRefPubMed
32.
go back to reference Cao Y, Linden P, Shima D, Browne F, Folkman J: In vivo angiogenic activity and hypoxia induction of heterodimers of placenta growth factor/vascular endothelial growth factor. J Clin Invest 1996,98(11):2507–2511. 10.1172/JCI119069PubMedCentralCrossRefPubMed Cao Y, Linden P, Shima D, Browne F, Folkman J: In vivo angiogenic activity and hypoxia induction of heterodimers of placenta growth factor/vascular endothelial growth factor. J Clin Invest 1996,98(11):2507–2511. 10.1172/JCI119069PubMedCentralCrossRefPubMed
33.
go back to reference de Bruin M, Smid K, Laan AC, Noordhuis P, Fukushima M, Hoekman K, Pinedo HM, Peters GJ: Rapid disappearance of deoxyribose-1-phosphate in platelet derived endothelial cell growth factor/thymidine phosphorylase overexpressing cells. Biochem Biophys Res Commun 2003,301(3):675–679. 10.1016/S0006-291X(03)00022-6CrossRefPubMed de Bruin M, Smid K, Laan AC, Noordhuis P, Fukushima M, Hoekman K, Pinedo HM, Peters GJ: Rapid disappearance of deoxyribose-1-phosphate in platelet derived endothelial cell growth factor/thymidine phosphorylase overexpressing cells. Biochem Biophys Res Commun 2003,301(3):675–679. 10.1016/S0006-291X(03)00022-6CrossRefPubMed
34.
go back to reference Folkman J: What is the role of thymidine phosphorylase in tumor angiogenesis. J Natl Cancer Inst 1996,88(16):1091–1092. 10.1093/jnci/88.16.1091CrossRefPubMed Folkman J: What is the role of thymidine phosphorylase in tumor angiogenesis. J Natl Cancer Inst 1996,88(16):1091–1092. 10.1093/jnci/88.16.1091CrossRefPubMed
35.
go back to reference Fujiwaki R, Hata K, Nakayama K, Fukumoto M, Miyazaki K: Thymidylatesynthase expression in epithelial ovarian cancer: relationship with thymidine phosphorylase expression and prognosis. Oncology 2000,59(2):152–157. 10.1159/000012153CrossRefPubMed Fujiwaki R, Hata K, Nakayama K, Fukumoto M, Miyazaki K: Thymidylatesynthase expression in epithelial ovarian cancer: relationship with thymidine phosphorylase expression and prognosis. Oncology 2000,59(2):152–157. 10.1159/000012153CrossRefPubMed
36.
go back to reference Tsukagoshi S, Saga Y, Suzuki N, Fujioka A, Nakagawa F, Fukushima M, Suzuki M: Thymidine phosphorylase-mediated angiogenesis regulated by thymidine phosphorylase inhibitor in human ovarian cancer cells in vivo. Int J Oncol 2003,22(5):961–967.PubMed Tsukagoshi S, Saga Y, Suzuki N, Fujioka A, Nakagawa F, Fukushima M, Suzuki M: Thymidine phosphorylase-mediated angiogenesis regulated by thymidine phosphorylase inhibitor in human ovarian cancer cells in vivo. Int J Oncol 2003,22(5):961–967.PubMed
37.
go back to reference Kitazono M, Takebayashi Y, Ishitsuka K, Takao S, Tani A, Furukawa T, Miyadera K, Yamada Y, Aikou T, Akiyama S: Prevention of hypoxia-induced poptosis by the angiogenic factor thymidine phosphorylase. Biochem Biophys Res Commun 1998,253(3):797–803. 10.1006/bbrc.1998.9852CrossRefPubMed Kitazono M, Takebayashi Y, Ishitsuka K, Takao S, Tani A, Furukawa T, Miyadera K, Yamada Y, Aikou T, Akiyama S: Prevention of hypoxia-induced poptosis by the angiogenic factor thymidine phosphorylase. Biochem Biophys Res Commun 1998,253(3):797–803. 10.1006/bbrc.1998.9852CrossRefPubMed
38.
go back to reference Jeung HC, Che XF, Haraguchi M, Furukawa T, Zheng CL, Sumizawa T, Rha SY, Roh JK, Akiyama S: Thymidine phosphorylase suppresses apoptosis induced by microtubule-interfering agents. Biochem Pharmacol 2005,70(1):13–21. 10.1016/j.bcp.2005.04.017CrossRefPubMed Jeung HC, Che XF, Haraguchi M, Furukawa T, Zheng CL, Sumizawa T, Rha SY, Roh JK, Akiyama S: Thymidine phosphorylase suppresses apoptosis induced by microtubule-interfering agents. Biochem Pharmacol 2005,70(1):13–21. 10.1016/j.bcp.2005.04.017CrossRefPubMed
39.
go back to reference Ko JC, Chiu HC, Syu JJ, Jian YJ, Chen CY, Jian YT, Huang YJ, Wo TY, Lin YW: Tamoxifen enhances erlotinib-induced cytotoxicity through down-regulating AKT-mediated thymidine phosphorylase expression in human non-small-cell lung cancer cells. Biochem Pharmacol 2014,88(1):119–127. 10.1016/j.bcp.2014.01.010CrossRefPubMed Ko JC, Chiu HC, Syu JJ, Jian YJ, Chen CY, Jian YT, Huang YJ, Wo TY, Lin YW: Tamoxifen enhances erlotinib-induced cytotoxicity through down-regulating AKT-mediated thymidine phosphorylase expression in human non-small-cell lung cancer cells. Biochem Pharmacol 2014,88(1):119–127. 10.1016/j.bcp.2014.01.010CrossRefPubMed
Metadata
Title
4-Methylumbelliferone inhibits ovarian cancer growth by suppressing thymidine phosphorylase expression
Authors
Ryosuke Tamura
Yoshihito Yokoyama
Hidemi Yoshida
Tadaatsu Imaizumi
Hideki Mizunuma
Publication date
01-12-2014
Publisher
BioMed Central
Published in
Journal of Ovarian Research / Issue 1/2014
Electronic ISSN: 1757-2215
DOI
https://doi.org/10.1186/s13048-014-0094-2

Other articles of this Issue 1/2014

Journal of Ovarian Research 1/2014 Go to the issue