Cortex Moutan Inhibits Bladder Cancer Cell Proliferation and Expression of Angiogenic Factors

Mei-Yi Lin, Cheng-Huang Shen, Su-Yin Chiang, Syue-Yi Chen, Yu-Shih Lin, Cheng-Da Hsu

Department of Chinese Medicine Pharmacy, Chiayi Chang Gung Memorial Hospital, Chia-Yi, Taiwan.
Department of Medical Research, Ditmanson Medical Foundation Chia-Yi Christian Hospital, Chia-Yi, Taiwan.
Department of Medical Research, Ditmanson Medical Foundation Chia-Yi Christian Hospital, Chia-Yi, Taiwan Department of Urology, Ditmanson Medical Foundation Chia-Yi Christian Hospital, Chia-Yi, Taiwan.
Graduate Institute of Chinese Medicine, College of Chinese Medicine, China Medical University, Taichung, Taiwan.
Graduate Institute of Chinese Medicine, College of Chinese Medicine, China Medical University, Taichung, Taiwan Department of Chinese Medicine, Ditmanson Medical Foundation Chia-Yi Christian Hospital, Chia-Yi, Taiwan.

DOI: 10.4236/pp.2014.58095                

Abstract

Metastases are the main cause of death among patients with bladder cancer, which is the second most common malignancy of the genitourinary tract and is highly prevalent in the southwestern region of Taiwan. Angiogenesis plays a critical role in tumor growth and metastasis processes and has relevance in disease recurrence, pelvic lymph node metastasis and poor prognosis. Cancer cells can produce several angiogenesis-stimulating factors involved in vascular growth, including vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), and inflammatory cytokines such as interleukin (IL)-8. Common chemotherapeutic drugs for intravesical instillations usually cause major side effects, including urinary frequency, urinary urgency, cystitis, and hematuria. In order to identify a less cytotoxic therapeutic agent that can inhibit tumor cell proliferation, we examined the traditional Chinese herbal medicine Cortex Moutan—reported to have antibacterial, antiviral, anti-inflammatory, antithrombotic, and antitumor properties—for its effects on bladder cancer cell proliferation and expression of angiogenic factors. Our results revealed that Cortex Moutan exhibited high selectivity in inhibiting the growth of bladder cancer cells and also reduced the expression of angiogenesis-stimulating factors in those cells. Thus, we suggest that Cortex Moutan might be used as a cancer therapy drug for bladder’s intravesical chemotherapy in the future.

Keywords

Cortex Moutan, BFTC 905 Cells, TSGH 8301 Cells, Growth Inhibition, VEGF, bFGF, IL-8

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1]	Oosterlinck, W., Solsona, E., van der Meijden, A.P., Sylvester, R., Bohle, A., Rintala, E. and Lobel, B. (2004) EAU Guidelines on Diagnosis and Treatment of Upper Urinary Tract Transitional Cell Carcinoma. European Urology, 46, 147-154. http://dx.doi.org/10.1016/j.eururo.2004.04.011
[2]	Heney, N.M. (1992) Natural History of Superficial Bladder Cancer. Prognostic Features and Long-Term Disease Course. Urologic Clinics of North America, 19, 429-433.
[3]	Roupret, M., Zigeuner, R., Palou, J., Boehle, A., Kaasinen, E., Sylvester, R., Babjuk, M. and Oosterlinck, W. (2012) European Guidelines for the Diagnosis and Management of Upper Urinary Tract Urothelial Cell Carcinomas: 2011 Update. Actas Urológicas Españolas, 36, 2-14. http://dx.doi.org/10.1016/j.acuro.2011.09.001
[4]	Lower Jr., G.M. (1982) Concepts in Causality: Chemically Induced Human Urinary Bladder Cancer. Cancer, 49, 1056-1066. http://dx.doi.org/10.1002/1097-0142(19820301)49:5<1056::AID-CNCR2820490535>3.0.CO;2-I
[5]	Burger, M.S., Torino, J.L. and Swaminathan, S. (2001) DNA Damage in Human Transitional Cell Carcinoma Cells after Exposure to the Proximate Metabolite of the Bladder Carcinogen 4-Aminobiphenyl. Environmental and Molecular Mutagenesis, 38, 1-11. http://dx.doi.org/10.1002/em.1044
[6]	Tan, L.B., Chen, K.T. and Guo, H.R. (2008) Clinical and Epidemiological Features of Patients with Genitourinary Tract Tumour in a Blackfoot Disease Endemic Area of Taiwan. BJU International, 102, 48-54. http://dx.doi.org/10.1111/j.1464-410X.2008.07565.x
[7]	Yang, C.Y., Chiu, H.F., Chang, C.C., Ho, S.C. and Wu, T.N. (2005) Bladder Cancer Mortality Reduction after Installation of a Tap-Water Supply System in an Arsenious-Endemic Area in Southwestern Taiwan. Environmental Research, 98, 127-132. http://dx.doi.org/10.1016/j.envres.2004.07.013
[8]	Wallerand, H., Bakkar, A.A., de Medina, S.G., Pairon, J.C., Yang, Y.C., Vordos, D., Bittard, H., Fauconnet, S., Kouyoumdjian, J.C., Jaurand, M.C., et al. (2005) Mutations in TP53, but Not FGFR3, in Urothelial Cell Carcinoma of the Bladder Are Influenced by Smoking: Contribution of Exogenous Versus Endogenous Carcinogens. Carcinogenesis, 26, 177-184. http://dx.doi.org/10.1093/carcin/bgh275
[9]	Spiess, P.E. and Czerniak, B. (2006) Dual-Track Pathway of Bladder Carcinogenesis: Practical Implications. Archives of Pathology & Laboratory Medicine, 130, 844-852.
[10]	Barocas, D.A. and Clark, P.E. (2008) Bladder Cancer. Current Opinion in Oncology, 20, 307-314. http://dx.doi.org/10.1097/CCO.0b013e3282f8b03e
[11]	Chen, C.H., Yang, H.J., Shun, C.T., Huang, C.Y., Huang, K.H., Yu, H.J. and Pu, Y.S. (2010) A Cocktail Regimen of Intravesicalmitomycin-C, Doxorubicin, and Cisplatin (MDP) for Non-Muscle-Invasive Bladder Cancer. Urologic Oncology, 30, 421-427. http://dx.doi.org/10.1016/j.urolonc.2010.06.012
[12]	Afonso, J., Santos, L.L., Amaro, T., Lobo, F. and Longat-to-Filho, A. (2009) The Aggressiveness of Urothelial Carcinoma Depends to a Large Extent on Lymphovascular Invasion—The Prognostic Contribution of Related Molecular Markers. Histopathology, 55, 514-524. http://dx.doi.org/10.1111/j.1365-2559.2009.03425.x
[13]	Inoue, K., Slaton, J.W., Karashima, T., Yoshikawa, C., Shuin, T., Sweeney, P., Millikan, R. and Dinney, C.P. (2000) The Prognostic Value of Angiogenesis Factor Expression for Predicting Recurrence and Metastasis of Bladder Cancer after Neoadjuvant Chemotherapy and Radical Cystectomy. Clinical Cancer Research, 6, 4866-4873.
[14]	O’Brien, T., Cranston, D., Fuggle, S., Bicknell, R. and Harris, A.L. (1995) Different Angiogenic Pathways Characterize Superficial and Invasive Bladder Cancer. Cancer Research, 55, 510-513.
[15]	Suzuki, K., Morita, T. and Tokue, A. (2005) Vascular Endothelial Growth Factor-C (VEGF-C) Expression Predicts Lymph Node Metastasis of Transitional Cell Carcinoma of the blaDder. International Journal of Urology, 12, 152-158. http://dx.doi.org/10.1111/j.1442-2042.2005.01010.x
[16]	Black, P.C. and Dinney, C.P. (2007) Bladder Cancer Angiogenesis and Metastasis—Translation from Murine Model to Clinical Trial. Cancer and Metastasis Reviews, 26, 623-634. http://dx.doi.org/10.1007/s10555-007-9084-9
[17]	Xu, S.J., Yang, L., Zeng, X., Zhang, M. and Wang, Z.T. (2006) Characterization of Compounds in the Chinese Herbal Drug Mu-Dan-Pi by Liquid Chromatography Coupled to Electrospray Ionization Mass Spectrometry. Rapid Communications in Mass Spectrometry, 20, 3275-3288. http://dx.doi.org/10.1002/rcm.2717
[18]	Sun, G.P., Shen, Y.X., Zhang, L.L., Zhou, A.W., Wei, W. and Xu, S.Y. (2003) Research on Immunomodulatory and Antitumor Effects of Paeonol in a Mouse Model of HepA Hepatoma. Journal of Chinese Pharmaceutical Sciences, 19, 160-162.
[19]	Sun, G.P., Shen, Y.X., Zhang, L.L., Wang, H., Wei, W. and Xu, S.Y. (2002) In Vitro Antitumor Effects of Paeonol. Acta Universitis Medicinalis Anhui, 37, 183-185.
[20]	Ji, C.Y., Tan, S.Y. and Liu, C.Q. (2005) Effects of Paeonol on Apoptosis, Cell Cycle, and Patient Prognosis in Human Colon Cancer. Chinese Journal of Clinical Rehabilitation, 9, 122-124.
[21]	Xu, S.P., Sun, G.P., Shen, Y.X., Wei, W., Peng, W.R. and Wang, H. (2007) Antiproliferation and Apoptosis Induction of Paeonol in HepG2 Cells. World Journal of Gastroenterology, 13, 250-256. http://dx.doi.org/10.3748/wjg.v13.i2.250
[22]	Sun, G.P., Wan, X., Xu, S.P., Wang, H., Liu, S.H. and Wang, Z.G. (2008) Antiproliferation and Apoptosis Induction of Paeonol in Human Esophageal Cancer Cell Lines. Diseases of the Esophagus, 21, 723-729. http://dx.doi.org/10.1111/j.1442-2050.2008.00840.x
[23]	Lee, H.J., Kim, S.A., Jeong, S.J., Han, I., Jung, J.H., Lee, E.O., Zhu, S., Chen, C.Y. and Kim, S.H. (2010) Paeonol Oxime Inhibits bFGF-Induced Angiogenesis and Reduces VEGF Levels in Fibrosarcoma Cells. PLoS ONE, 5, Article ID: e12358. http://dx.doi.org/10.1371/journal.pone.0012358
[24]	Lin, M.Y., Lee, Y.R., Chiang, S.Y., Li, Y.Z., Chen, Y.S., Hsu, C.D. and Liu, Y.W. (2013) Cortex Moutan Induces Bladder Cancer Cell Death via Apoptosis and Retards Tumor Growth in Mouse Bladders. Evidence-Based Complementary and Alternative Medicine, 2013, Article ID: 207279, 8 p. http://dx.doi.org/10.1155/2013/207279
[25]	Oh, G.S., Pae, H.O., Choi, B.M., Lee, H.S., Kim, I.K., Yun, Y.G., Kim, J.D. and Chung, H.T. (2004) Penta-O-galloyl-β-D-Glucose Inhibits Phorbol Myristate Acetate-Induced Interleu-kin-8 [Correction of Intereukin-8] Gene Expression in Human Monocytic U937 Cells through Its Inactivation of Nuclear Factor-κB. International Immunopharmacology, 4, 377-386. http://dx.doi.org/10.1016/j.intimp.2003.10.010
[26]	Choi, H.S., Seo, H.S., Kim, J.H., Um, J.Y., Shin, Y.C. and Ko, S.G. (2012) Ethanol Extract of Paeonia suffruticosa Andrews (PSE) Induced AGS Human Gastric Cancer Cell Apoptosis via Fas-Dependent Apoptosis and MDM2-p53 Pathways. Journal of Biomedical Science, 19, 82. http://dx.doi.org/10.1186/1423-0127-19-82
[27]	Wang, S.C., Tang, S.W., Lam, S.H., Wang, C.C., Liu, Y.H., Lin, H.Y., Lee, S.S. and Lin, J.Y. (2012) Aqueous Extract of Paeonia Suffruticosa Inhibits Migration and Metastasis of Renal Cell Carcinoma Cells via Suppressing VEGFR-3 Pathway. Evidence-Based Complementary and Alternative Medicine, 2012, Article ID: 409823.
[28]	Hsu, C.D., Chen, S.Y., Hung, L.C., Lin, C.P. and Lin, M.Y. (2010) The Effect of Cortex Mouta on Human Umbilical Vein Endotheial Cells and Epithelial Tumor Cells. Journal of Integrated Chinese and Western Medicine, 12, 1-9.
[29]	Prayong, P., Barusrux, S. and Weerapreeyakul, N. (2008) Cytotoxic Activity Screening of Some Indigenous Thai Plants. Fitoterapia, 79, 598-601. http://dx.doi.org/10.1016/j.fitote.2008.06.007
[30]	Hartwell, L.H. and Kastan, M.B. (1994) Cell Cycle Control and Cancer. Science, 266, 1821-1828. http://dx.doi.org/10.1126/science.7997877
[31]	Vermeulen, K., Berneman, Z.N. and Van Bockstaele, D.R. (2003) Cell Cycle and Apoptosis. Cell Proliferation, 36, 165-175. http://dx.doi.org/10.1046/j.1365-2184.2003.00267.x
[32]	Li, N., Fan, L.L., Sun, G.P., Wan, X.A., Wang, Z.G., Wu, Q., Wang, H. (2010) Paeonol Inhibits Tumor Growth in Gastric Cancer in Vitro and in Vivo. World Journal of Gastroenterology, 16, 4483-4490. http://dx.doi.org/10.3748/wjg.v16.i35.4483
[33]	Cheng, Y.J., Jiang, H.S., Hsu, S.L., Lin, L.C., Wu, C.L., Ghanta, V.K. and Hsueh, C.M. (2010) XIAP-Mediated Protection of H460 Lung Cancer Cells against Cisplatin. European Journal of Pharmacology, 627, 75-84. http://dx.doi.org/10.1016/j.ejphar.2009.11.003
[34]	Lu, C.C., Lin, M.Y., Chen, S.Y., Shen, C.H., Chen, L.G., Hsieh, H.Y., Chan, M.W. and Hsu, C.D. (2013) The Investigation of a Traditional Chinese Medicine, Guizhi Fuling Wan (GFW) as an Intravesical Therapeutic Agent for Urothelial Carcinoma of the Bladder. BMC Complementary and Alternative Medicine, 13, 44. http://dx.doi.org/10.1186/1472-6882-13-44
[35]	Pandya, N.M., Dhalla, N.S. and Santani, D.D. (2006) Angiogenesis—A New Target for Future Therapy. Vascular Pharmacology, 44, 265-274. http://dx.doi.org/10.1016/j.vph.2006.01.005
[36]	Koch, A.E., Polverini, P.J., Kunkel, S.L., Harlow, L.A., DiPietro, L.A., Elner, V.M., Elner, S.G. and Strieter, R.M. (1992) Interleukin-8 as a Macrophage-Derived Mediator of Angiogenesis. Science, 258, 1798-1801. http://dx.doi.org/10.1126/science.1281554
[37]	Dvorak, H.F., Brown, L.F., Detmar, M. and Dvorak, A.M. (1995) Vascular Permeability Factor/Vascular Endothelial Growth Factor, Microvascular Hyperpermeability, and Angiogenesis. American Journal of Pathology, 146, 1029-1039.