Apoptosis of Human Bladder Cancer Cells by an Ethanolic Extract of Scutellaria Baicalensis GEORGI Via Caspase and MAPK Signaling Pathways
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An ethanolic extracts of Scutellaria Baicalensis GEORGI are used to treat cancer, infectious diseases, and inflammation. In the present study, we investigated the effects of an ESBG on the growth and survival of 5637 cells, a human bladder carcinoma cell line. Cells were treated with different concentrations of an ethanolic extract of Scutellaria Baicalensis GEORGI (ESBG), and cell death was assessed using a MTT (3-[4, 5-dimethylthiazol-2-yl]-2, 5-diphenyltetrazolium bromide) assay. Analyses of the sub G1 peak, caspase-3 and -9 activities, and mitochondrial membrane depolarizations were conducted to confirm cell death by apoptosis. ESBG had a cytotoxic effect on 5637 cells, and increased the sub G1 peak, caspase-3 and -9 activities, and mitochondrial depolarization, indicating ESBG induced apoptosis. Furthermore, MAPK (mitogen-activated protein kinases) inhibitors suppressed this apoptosis. In an in vitro study, a combination of sub-optimal doses of ESBG and paclitaxel, 5-fluorouracil, or docetaxel noticeably suppressed tumor growth by 5637 cells. Our findings provide insight of the mechanisms underlying cellular apoptosis induced by ESBG, and suggest new therapeutic strategies for bladder cancer.
Abstract
An ethanolic extracts of Scutellaria Baicalensis GEORGI are used to treat cancer, infectious diseases, and inflammation. In the present study, we investigated the effects of an ESBG on the growth and survival of 5637 cells, a human bladder carcinoma cell line. Cells were treated with different concentrations of an ethanolic extract of Scutellaria Baicalensis GEORGI (ESBG), and cell death was assessed using a MTT (3-[4, 5-dimethylthiazol-2-yl]-2, 5-diphenyltetrazolium bromide) assay. Analyses of the sub G1 peak, caspase-3 and -9 activities, and mitochondrial membrane depolarizations were conducted to confirm cell death by apoptosis. ESBG had a cytotoxic effect on 5637 cells, and increased the sub G1 peak, caspase-3 and -9 activities, and mitochondrial depolarization, indicating ESBG induced apoptosis. Furthermore, MAPK (mitogen-activated protein kinases) inhibitors suppressed this apoptosis. In an in vitro study, a combination of sub-optimal doses of ESBG and paclitaxel, 5-fluorouracil, or docetaxel noticeably suppressed tumor growth by 5637 cells. Our findings provide insight of the mechanisms underlying cellular apoptosis induced by ESBG, and suggest new therapeutic strategies for bladder cancer.
참고문헌 (27)
- Guo, Q., "Effect and Molecular Mechanisms of Traditional Chinese Medicine on Regulating Tumor Immunosuppressive Microenvironment", Biomed Res Int, 2015, pp.261620~ (2015)
- Li, J., "Integrative medicine: a characteristic China model for cancer treatment", Chin J Integr Med, 17, pp.243~245 (2011)
- Li, J., "Establishing Chinesemedicine characteristic tumor response evaluation system is the key to promote internationalization of Chinese medicine oncology", Chin J Integr Med, 18, pp.730~736 (2012)
- National Pharmacopoeia Committee, "Phamacopoeia of People’s Republic of China", pp.159~160 (2010), Medical Science and Technology Publishing House
- Li-Weber, M., "New therapeutic aspects of flavones: the anticancer properties of Scutellaria and its main active constituents Wogonin, Baicalein and Baicalin", Cancer Treat Rev, 35, pp.57~68 (2009)
- Zhang, N., "A Herbal Composition of Scutellaria baicalensis and Eleutherococcus senticosus Shows Potent Anti-Inflammatory Effects in an Ex Vivo Human Mucosal Tissue Model", Evid Based Complement Altern Med, 2012, pp.673145~ (2012)
- Guo, Q., "Anti-hepatitis B virus activity of wogonin in vitro and in vivo", Antiviral Res, 74, pp.16~24 (2007)
- Kowalczyk, E., "Pharmacological effects of flavonoids from Scutellaria baicalensis", Przegl Lek, 63, pp.95~96 (2006)
- Li, C., "Pharmacological effects and pharmacokinetics properties of Radix Scutellariae and its bioactive flavones", Biopharm Drug Dispos, 32, pp.427~445 (2011)
- Liao, J. F., "Anxiolytic-like effects of baicalein and baicalin in the Vogel conflict test in mice", Eur J Pharmacol, 464, pp.141~146 (2003)
- Zhang, Q., "Application of ionic liquid-based microwave-assisted extraction of flavonoids from Scutellaria baicalensis Georgi", J Chromatogr B Analyt Technol Biomed Life Sci, 1002, pp.411~417 (2015)
- Majno, G., "Apoptosis, oncosis, and necrosis. An overview of cell death", Am J Pathol, 146, pp.3~15 (1995)
- Saraste, A., "Morphologic and biochemical hallmarks of apoptosis", Cardiovasc Res, 45, pp.528~537 (2000)
- Nicoletti, I., "A rapid and simple method for measuring thymocyte apoptosis by propidium iodide staining and flow cytometry", J Immunol Methods, 139, pp.271~279 (1991)
- Hellein, K. N., "A filter-based propidium monoazide technique to distinguish live from membrane-compromised microorganisms using quantitative PCR", J Microbiol Methods, 89, pp.76~78 (2012)
- Wang, B. J., "Free radical scavenging and apoptotic effects of Cordyceps sinensis fractionated by supercritical carbon dioxide", Food Chem Toxicol, 43, pp.543~552 (2005)
- Lee, S. J., "Aqueous extract of Magnolia officinalis mediates proliferative capacity, p21WAF1 expression and TNF-alpha-induced NF-kappaB activity in human urinary bladder cancer 5637 cells; involvement of p38 MAP kinase", Oncol Rep, 18, pp.729~736 (2007)
- Tang, W., "Chinese drug of plant origin: chemistry, pharmacology and use in traditional and modern medicine", pp.919~929 (1992), Springer-Verlag
- Kumagai, T., "Scutellaria baicalensis, a herbal medicine: anti-proliferative and apoptotic activity against acute lymphocytic leukemia, lymphoma and myeloma cell lines", Leukemia Res, 31, pp.523~530 (2007)
- Yune, T. Y., "Neuroprotective effect of Scutellaria baicalensis on spinal cord injury in rats", J Neurochem, 110, pp.1276~1287 (2009)
- R.M. Levy, "A Medicinal Extract of Scutellaria baicalensis and Acacia catechu Acts as a Dual Inhibitor of Cyclooxygenase and 5-Lipoxygenase to Reduce Inflammation", Journal of Medicinal Food, 10(3), pp.442~451 (2007), 한국식품영양과학회
- Shin, H. S., "Preventive effects of skull cap (Scutellaria baicalensis) extract in a mouse model of food allergy", J Ethnopharmacol, 153, pp.667~673 (2014)
- Saraste, A., "Morphologic and biochemical hallmarks of apoptosis", Cardiovasc Res, 45, pp.528~537 (2000)
- Sheikh, M. S., "Death receptors as targets of cancer therapeutics", Curr Cancer Drug Targets, 4, pp.97~104 (2004)
- Murphy, L. O., "MAPK signal specificity: the right place at the right time", Trends Biochem Sci, 31, pp.268~275 (2006)
- Fan, M., "Role of mitogen-activated protein kinases in the response of tumor cells to chemotherapy", Drug Resist Updat, 4, pp.253~267 (2001)
- Chen, D., "Capsaicin induces cycle arrest by inhibiting cyclin-dependent-kinase in bladder carcinoma cells", Int J Urol, 19, pp.662~668 (2012)