研究生: |
王天駿 Tien-Chun Wang |
---|---|
論文名稱: |
以A549肺癌細胞株為模式篩選對非小細胞肺癌有治療潛力之中藥複方 Screening of potential Chinese herbal formulae for non-small-cell lung cancer through carcinoma cell line A549 |
指導教授: |
謝秀梅
Hsieh, Hsiu-Mei |
學位類別: |
碩士 Master |
系所名稱: |
生命科學系 Department of Life Science |
論文出版年: | 2010 |
畢業學年度: | 98 |
語文別: | 英文 |
論文頁數: | 71 |
中文關鍵詞: | A549 、非小細胞肺癌 、中藥 、細胞週期 、癌幹細胞 、側群細胞 |
英文關鍵詞: | A549, NSCLC, CHM, cell cycle, CSC, side population |
論文種類: | 學術論文 |
相關次數: | 點閱:405 下載:11 |
分享至: |
查詢本校圖書館目錄 查詢臺灣博碩士論文知識加值系統 勘誤回報 |
肺癌長期以來都是全世界致死率最高的癌症疾病。根據型態上和病理上的特徵分類之結果,絕大多數的肺癌病例屬於非小細胞肺癌。雖然現今已經發展出許多針對癌症的治療方法,卻依然沒有可以確實治癒癌症的方法。我們利用非小細胞肺癌細胞株A549為模式,篩檢十五種臨床上常用的中藥複方,期能找出能有效治療肺癌的替代性藥物。在細胞毒性的初步篩檢中,我們挑出三種可以有效抑制A549細胞生長卻不影響正常肺部組織細胞MRC5的中藥複方,分別是三號、五號及十四號藥方。在進一步的分析中發現,此三種複方的處理會造成A549細胞週期停滯進而抑制細胞的生長,但不會顯著地造成細胞死亡,同時我們也發現在經由三種複方的處理後,cyclin D3、cyclin B1、CDK4和CDK6這些細胞週期調控蛋白的表現,有顯著下降的現象,得到與細胞週期停滯現象一致之結果。此外,我們也發現三號及五號複方能有效地減少具有癌幹細胞特性的側群細胞(side population)的比率,而這個現象似乎與間葉表皮轉換(Mesenchymal to epithelial transition)的機制無關。我們也試著藉由檢測血管內皮新生因子A (VEGF-A)表現量去應證這些在中醫理論中具有活血化瘀效用的藥方是否對於癌症細胞分泌促血管增生因子的行為有調節的效用。本實驗的結果提供了分子生物學上的證據去解釋這些複方在臨床上可能的治病機轉以及中醫理論在分子生物學上的意義,更重要的是,我們發現三個中藥複方具有可以被用來抑制非小細胞肺癌細胞之潛力。
Lung cancer has long been one of the most deadly diseases all over the world. According to the morphological and pathological classification, the majority of lung cancers are belonged to non-small cell lung cancer (NSCLC). Although there are a lot of therapeutic approaches toward cancers, none of the treatments can substantially cure patients suffering from cancers till now. Here we use non-small cell lung carcinoma cell line A549 to screen 15 different traditional Chinese herbal medicine (CHM) formulae to explore the possibility of alternative medicine. In this study, we identified three potential formulae could substantially decreased the survival of A549 cells and not affect normal lung tissue cells MRC5. Flow cytometry analysis showed that treatment of the three formulae induced cell cycle arrest in G1 (formulae 3, 5, and 14) and G2 phase (only formula 14) without causing significant cell death. These results were also confirmed by western blot analysis showed decreased expression of G1/S and G2/M promoting cell cycle machinery including cyclin D3, cyclin B1, CDK4, and CDK6. In addition, formulae 3 and 5 were also demonstrated to be able to reduce the stem-like cancer cells side population (SP) and the mesenchymal to epithelial transition (MET) process is not involved in the diminishing of SP cells. We also analyzed the expression of VEGF-A to examine whether the angiogenic effect of A549 cancer cells would be influenced by these CHM formulae. This study provides direct evidences to explain the possible formula working mechanism toward patients and also gives molecular biological evidences demonstrated the perspective of TCM theory. Most importantly, we identified three potential formulae which could be used in NSCLC diseases.
Adams, L.S., Seeram, N.P., Hardy, M.L., Carpenter, C., and Heber, D. (2006). Analysis of the interactions of botanical extract combinations against the viability of prostate cancer cell lines. Evid Based Complement Alternat Med 3, 117-124.
Al-Hajj, M., Wicha, M.S., Benito-Hernandez, A., Morrison, S.J., and Clarke, M.F. (2003). Prospective identification of tumorigenic breast cancer cells. Proc Natl Acad Sci U S A 100, 3983-3988.
Aung, H.H., Dey, L., Mehendale, S., Xie, J.T., Wu, J.A., and Yuan, C.S. (2003). Scutellaria baicalensis extract decreases cisplatin-induced pica in rats. Cancer Chemother Pharmacol 52, 453-458.
Biesalski, H.K., Bueno de Mesquita, B., Chesson, A., Chytil, F., Grimble, R., Hermus, R.J., Kohrle, J., Lotan, R., Norpoth, K., Pastorino, U., et al. (1998). European Consensus Statement on Lung Cancer: risk factors and prevention. Lung Cancer Panel. CA Cancer J Clin 48, 167-176; discussion 164-166.
Blagosklonny, M.V., and Pardee, A.B. (2002). The restriction point of the cell cycle. Cell Cycle 1, 103-110.
Catelinois, O., Rogel, A., Laurier, D., Billon, S., Hemon, D., Verger, P., and Tirmarche, M. (2006). Lung cancer attributable to indoor radon exposure in france: impact of the risk models and uncertainty analysis. Environ Health Perspect 114, 1361-1366.
Chang, W.H., Chen, C.H., Gau, R.J., Lin, C.C., Tsai, C.L., Tsai, K., and Lu, F.J. (2002). Effect of baicalein on apoptosis of the human Hep G2 cell line was induced by mitochondrial dysfunction. Planta Med 68, 302-306.
Chang, Y.H., Kim, C., Jung, M., Lim, Y.H., Lee, S., and Kang, S. (2007). Inhibition of melanogenesis by selina-4(14),7(11)-dien-8-one isolated from Atractylodis Rhizoma Alba. Biol Pharm Bull 30, 719-723.
Chao, J.C., Chiang, S.W., Wang, C.C., Tsai, Y.H., and Wu, M.S. (2006). Hot water-extracted Lycium barbarum and Rehmannia glutinosa inhibit proliferation and induce apoptosis of hepatocellular carcinoma cells. World J Gastroenterol 12, 4478-4484.
Chen, Q., Wang, Y., Xu, K., Lu, G., Ying, Z., Wu, L., Zhan, J., Fang, R., Wu, Y., and Zhou, J. (2010). Curcumin induces apoptosis in human lung adenocarcinoma A549 cells through a reactive oxygen species-dependent mitochondrial signaling pathway. Oncol Rep 23, 397-403.
Chen, Y.L., Jian, M.H., Lin, C.C., Kang, J.C., Chen, S.P., Lin, P.C., Hung, P.J., Chen, J.R., Chang, W.L., Lin, S.Z., et al. (2008). The induction of orphan nuclear receptor Nur77 expression by n-butylenephthalide as pharmaceuticals on hepatocellular carcinoma cell therapy. Mol Pharmacol 74, 1046-1058.
Cheng, K.T., Hou, W.C., Huang, Y.C., and Wang, L.F. (2003). Baicalin induces differential expression of cytochrome C oxidase in human lung H441 cell. J Agric Food Chem 51, 7276-7279.
Cheng, Y.W., Chiou, H.L., Sheu, G.T., Hsieh, L.L., Chen, J.T., Chen, C.Y., Su, J.M., and Lee, H. (2001). The association of human papillomavirus 16/18 infection with lung cancer among nonsmoking Taiwanese women. Cancer Res 61, 2799-2803.
Chiba, T., Kita, K., Zheng, Y.W., Yokosuka, O., Saisho, H., Iwama, A., Nakauchi, H., and Taniguchi, H. (2006). Side population purified from hepatocellular carcinoma cells harbors cancer stem cell-like properties. Hepatology 44, 240-251.
Chiu, H.F., Cheng, M.H., Tsai, S.S., Wu, T.N., Kuo, H.W., and Yang, C.Y. (2006). Outdoor air pollution and female lung cancer in Taiwan. Inhal Toxicol 18, 1025-1031.
Choi, H.J., Seon, M.R., Lim, S.S., Kim, J.S., Chun, H.S., and Park, J.H. (2008). Hexane/ethanol extract of Glycyrrhiza uralensis licorice suppresses doxorubicin-induced apoptosis in H9c2 rat cardiac myoblasts. Exp Biol Med (Maywood) 233, 1554-1560.
Chou, C.C., Pan, S.L., Teng, C.M., and Guh, J.H. (2003). Pharmacological evaluation of several major ingredients of Chinese herbal medicines in human hepatoma Hep3B cells. Eur J Pharm Sci 19, 403-412.
Collado, M., and Serrano, M. (2006). The power and the promise of oncogene-induced senescence markers. Nat Rev Cancer 6, 472-476.
Coyle, Y.M., Minahjuddin, A.T., Hynan, L.S., and Minna, J.D. (2006). An ecological study of the association of metal air pollutants with lung cancer incidence in Texas. J Thorac Oncol 1, 654-661.
Fang, D., Nguyen, T.K., Leishear, K., Finko, R., Kulp, A.N., Hotz, S., Van Belle, P.A., Xu, X., Elder, D.E., and Herlyn, M. (2005). A tumorigenic subpopulation with stem cell properties in melanomas. Cancer Res 65, 9328-9337.
Fauci, A.S., Harrison, T.R., and Teton Data Systems (Firm) (2008). Harrison's principles of internal medicine editors, Anthony S. Fauci ... [et al.] (New York, McGraw-Hill Medical).
Ferrara, N. (2004). Vascular endothelial growth factor: basic science and clinical progress. Endocr Rev 25, 581-611.
Ferrara, N., Gerber, H.P., and LeCouter, J. (2003). The biology of VEGF and its receptors. Nat Med 9, 669-676.
Gaube, F., Wolfl, S., Pusch, L., Kroll, T.C., and Hamburger, M. (2007). Gene expression profiling reveals effects of Cimicifuga racemosa (L.) NUTT. (black cohosh) on the estrogen receptor positive human breast cancer cell line MCF-7. BMC Pharmacol 7, 11.
Giuliani, L., Jaxmar, T., Casadio, C., Gariglio, M., Manna, A., D'Antonio, D., Syrjanen, K., Favalli, C., and Ciotti, M. (2007). Detection of oncogenic viruses SV40, BKV, JCV, HCMV, HPV and p53 codon 72 polymorphism in lung carcinoma. Lung Cancer 57, 273-281.
Gorlova, O.Y., Weng, S.F., Zhang, Y., Amos, C.I., and Spitz, M.R. (2007). Aggregation of cancer among relatives of never-smoking lung cancer patients. Int J Cancer 121, 111-118.
Guo, X.Z., and Song, C.L. (2002). The regulation of herbal application for lung cancer. Liaoning Journal of Traditional Chinese Medicine 2002. 29, 273.
Ha, K.T., Kim, J.K., Kang, S.K., Kim, D.W., Lee, Y.C., Kim, H.M., and Kim, C.H. (2004). Inhibitory effect of Sihoga-Yonggol-Moryo-Tang on matrix metalloproteinase-2 and -9 activities and invasiveness potential of hepatocellular carcinoma. Pharmacol Res 50, 279-285.
Hackshaw, A.K., Law, M.R., and Wald, N.J. (1997). The accumulated evidence on lung cancer and environmental tobacco smoke. BMJ 315, 980-988.
Hamilton, W., Peters, T.J., Round, A., and Sharp, D. (2005). What are the clinical features of lung cancer before the diagnosis is made? A population based case-control study. Thorax 60, 1059-1065.
Heald, R., and McKeon, F. (1990). Mutations of phosphorylation sites in lamin A that prevent nuclear lamina disassembly in mitosis. Cell 61, 579-589.
Hecht, S.S. (2003). Tobacco carcinogens, their biomarkers and tobacco-induced cancer. Nat Rev Cancer 3, 733-744.
Herbst, R.S., Heymach, J.V., and Lippman, S.M. (2008). Lung cancer. N Engl J Med 359, 1367-1380.
Hicklin, D.J., and Ellis, L.M. (2005). Role of the vascular endothelial growth factor pathway in tumor growth and angiogenesis. J Clin Oncol 23, 1011-1027.
Ho, M.M., Ng, A.V., Lam, S., and Hung, J.Y. (2007). Side population in human lung cancer cell lines and tumors is enriched with stem-like cancer cells. Cancer Res 67, 4827-4833.
Ho, Y.T., Yang, J.S., Li, T.C., Lin, J.J., Lin, J.G., Lai, K.C., Ma, C.Y., Wood, W.G., and Chung, J.G. (2009). Berberine suppresses in vitro migration and invasion of human SCC-4 tongue squamous cancer cells through the inhibitions of FAK, IKK, NF-kappaB, u-PA and MMP-2 and -9. Cancer Lett 279, 155-162.
Hostanska, K., Nisslein, T., Freudenstein, J., Reichling, J., and Saller, R. (2004). Cimicifuga racemosa extract inhibits proliferation of estrogen receptor-positive and negative human breast carcinoma cell lines by induction of apoptosis. Breast Cancer Res Treat 84, 151-160.
Houck, K.A., Ferrara, N., Winer, J., Cachianes, G., Li, B., and Leung, D.W. (1991). The vascular endothelial growth factor family: identification of a fourth molecular species and characterization of alternative splicing of RNA. Mol Endocrinol 5, 1806-1814.
Hsieh, T.C., Lu, X., Chea, J., and Wu, J.M. (2002). Prevention and management of prostate cancer using PC-SPES: a scientific perspective. J Nutr 132, 3513S-3517S.
Hsu, W.H., Hsieh, Y.S., Kuo, H.C., Teng, C.Y., Huang, H.I., Wang, C.J., Yang, S.F., Liou, Y.S., and Kuo, W.H. (2007). Berberine induces apoptosis in SW620 human colonic carcinoma cells through generation of reactive oxygen species and activation of JNK/p38 MAPK and FasL. Arch Toxicol 81, 719-728.
Hsu, Y.L., Cho, C.Y., Kuo, P.L., Huang, Y.T., and Lin, C.C. (2006). Plumbagin (5-hydroxy-2-methyl-1,4-naphthoquinone) induces apoptosis and cell cycle arrest in A549 cells through p53 accumulation via c-Jun NH2-terminal kinase-mediated phosphorylation at serine 15 in vitro and in vivo. J Pharmacol Exp Ther 318, 484-494.
Hsu, Y.L., Kuo, P.L., Tzeng, T.F., Sung, S.C., Yen, M.H., Lin, L.T., and Lin, C.C. (2008). Huang-lian-jie-du-tang, a traditional Chinese medicine prescription, induces cell-cycle arrest and apoptosis in human liver cancer cells in vitro and in vivo. J Gastroenterol Hepatol 23, e290-299.
Hu, C., Liu, H., Du, J., Mo, B., Qi, H., Wang, X., Ye, S., and Li, Z. (2009). Estrogenic activities of extracts of Chinese licorice (Glycyrrhiza uralensis) root in MCF-7 breast cancer cells. J Steroid Biochem Mol Biol 113, 209-216.
Hu, Y., Yang, Y., You, Q.D., Liu, W., Gu, H.Y., Zhao, L., Zhang, K., Wang, W., Wang, X.T., and Guo, Q.L. (2006). Oroxylin A induced apoptosis of human hepatocellular carcinoma cell line HepG2 was involved in its antitumor activity. Biochem Biophys Res Commun 351, 521-527.
Huang, D., Gao, Q., Guo, L., Zhang, C., Jiang, W., Li, H., Wang, J., Han, X., Shi, Y., and Lu, S.H. (2009a). Isolation and identification of cancer stem-like cells in esophageal carcinoma cell lines. Stem Cells Dev 18, 465-473.
Huang, H.P., Shih, Y.W., Wu, C.H., Lai, P.J., Hung, C.N., and Wang, C.J. (2009b). Inhibitory effect of penta-acetyl geniposide on C6 glioma cells metastasis by inhibiting matrix metalloproteinase-2 expression involved in both the PI3K and ERK signaling pathways. Chem Biol Interact 181, 8-14.
Iizuka, N., Miyamoto, K., Okita, K., Tangoku, A., Hayashi, H., Yosino, S., Abe, T., Morioka, T., Hazama, S., and Oka, M. (2000). Inhibitory effect of Coptidis Rhizoma and berberine on the proliferation of human esophageal cancer cell lines. Cancer Lett 148, 19-25.
Jang, J.Y., Lee, J.H., Kang, B.W., Chung, K.T., Choi, Y.H., and Choi, B.T. (2009). Dichloromethane fraction of Cimicifuga heracleifolia decreases the level of melanin synthesis by activating the ERK or AKT signaling pathway in B16F10 cells. Exp Dermatol 18, 232-237.
Jo, E.H., Hong, H.D., Ahn, N.C., Jung, J.W., Yang, S.R., Park, J.S., Kim, S.H., Lee, Y.S., and Kang, K.S. (2004). Modulations of the Bcl-2/Bax family were involved in the chemopreventive effects of licorice root (Glycyrrhiza uralensis Fisch) in MCF-7 human breast cancer cell. J Agric Food Chem 52, 1715-1719.
Jo, E.H., Kim, S.H., Ra, J.C., Kim, S.R., Cho, S.D., Jung, J.W., Yang, S.R., Park, J.S., Hwang, J.W., Aruoma, O.I., et al. (2005). Chemopreventive properties of the ethanol extract of chinese licorice (Glycyrrhiza uralensis) root: induction of apoptosis and G1 cell cycle arrest in MCF-7 human breast cancer cells. Cancer Lett 230, 239-247.
Jung, H.A., Min, B.S., Yokozawa, T., Lee, J.H., Kim, Y.S., and Choi, J.S. (2009). Anti-Alzheimer and antioxidant activities of Coptidis Rhizoma alkaloids. Biol Pharm Bull 32, 1433-1438.
Kabir, Z., Bennett, K., and Clancy, L. (2007). Lung cancer and urban air-pollution in Dublin: a temporal association? Ir Med J 100, 367-369.
Kang, J.X., Liu, J., Wang, J., He, C., and Li, F.P. (2005a). The extract of huanglian, a medicinal herb, induces cell growth arrest and apoptosis by upregulation of interferon-beta and TNF-alpha in human breast cancer cells. Carcinogenesis 26, 1934-1939.
Kang, K., Oh, Y.K., Choue, R., and Kang, S.J. (2005b). Scutellariae radix extracts suppress ethanol-induced caspase-11 expression and cell death in N(2)a cells. Brain Res Mol Brain Res 142, 139-145.
Kang, S.C., Lee, C.M., Choi, H., Lee, J.H., Oh, J.S., Kwak, J.H., and Zee, O.P. (2006). Evaluation of oriental medicinal herbs for estrogenic and antiproliferative activities. Phytother Res 20, 1017-1019.
Kang, S.W., Choi, J.S., Bae, J.Y., Li, J., Kim, D.S., Kim, J.L., Shin, S.Y., You, H.J., Park, H.S., Ji, G.E., et al. (2009). Blockade of vascular angiogenesis by Aspergillus usamii var. shirousamii-transformed Angelicae Gigantis Radix and Zizyphus jujuba. Nutr Res Pract 3, 3-8.
Khleif, S.N., DeGregori, J., Yee, C.L., Otterson, G.A., Kaye, F.J., Nevins, J.R., and Howley, P.M. (1996). Inhibition of cyclin D-CDK4/CDK6 activity is associated with an E2F-mediated induction of cyclin kinase inhibitor activity. Proc Natl Acad Sci U S A 93, 4350-4354.
Kim, D.C., Choi, S.Y., Kim, S.H., Yun, B.S., Yoo, I.D., Reddy, N.R., Yoon, H.S., and Kim, K.T. (2006). Isoliquiritigenin selectively inhibits H(2) histamine receptor signaling. Mol Pharmacol 70, 493-500.
Kimura, K., Hirano, M., Kobayashi, R., and Hirano, T. (1998). Phosphorylation and activation of 13S condensin by Cdc2 in vitro. Science 282, 487-490.
Lang, S.H., Frame, F.M., and Collins, A.T. (2009). Prostate cancer stem cells. J Pathol 217, 299-306.
Lee, H.J., Son, D.H., Lee, S.K., Lee, J., Jun, C.D., Jeon, B.H., and Kim, E.C. (2006). Extract of Coptidis rhizoma induces cytochrome-c dependent apoptosis in immortalized and malignant human oral keratinocytes. Phytother Res 20, 773-779.
Lee, J.H., Lee, D.U., and Jeong, C.S. (2009). Gardenia jasminoides Ellis ethanol extract and its constituents reduce the risks of gastritis and reverse gastric lesions in rats. Food Chem Toxicol.
Lee, J.W., Min, H.Y., Han, A.R., Chung, H.J., Park, E.J., Park, H.J., Hong, J.Y., Seo, E.K., and Lee, S.K. (2007). Growth inhibition and induction of G1 phase cell cycle arrest in human lung cancer cells by a phenylbutenoid dimer isolated from Zingiber cassumunar. Biol Pharm Bull 30, 1561-1564.
Lee, W.R., Shen, S.C., Lin, H.Y., Hou, W.C., Yang, L.L., and Chen, Y.C. (2002). Wogonin and fisetin induce apoptosis in human promyeloleukemic cells, accompanied by a decrease of reactive oxygen species, and activation of caspase 3 and Ca(2+)-dependent endonuclease. Biochem Pharmacol 63, 225-236.
Li, C., Heidt, D.G., Dalerba, P., Burant, C.F., Zhang, L., Adsay, V., Wicha, M., Clarke, M.F., and Simeone, D.M. (2007). Identification of pancreatic cancer stem cells. Cancer Res 67, 1030-1037.
Li, P.W. (2001). Comprehensive diagnosis and treatment for LC. Beijing: China Chinese Medicine Press, 2001: 561-589.
Li, Q., Cheng, H., Zhu, G., Yang, L., Zhou, A., Wang, X., Fang, N., Xia, L., Su, J., Wang, M., et al. (2010). Gambogenic acid inhibits proliferation of A549 cells through apoptosis-inducing and cell cycle arresting. Biol Pharm Bull 33, 415-420.
Liu, C.A., and M., P. (1994). Dictionary of Chinese anti-cancer herbal medicine. Hubei: Hubei Science and Technology Press, 1994: Tumor Index 31-33.
Liu, S., Ma, Z., Cai, H., Li, Q., Rong, W., and Kawano, M. (2009). Inhibitory effect of baicalein on IL-6-mediated signaling cascades in human myeloma cells. Eur J Haematol 84, 137-144.
Liu, Y., Jia, Z., Dong, L., Wang, R., and Qiu, G. (2008). A Randomized Pilot Study of Atractylenolide I on Gastric Cancer Cachexia Patients. Evid Based Complement Alternat Med 5, 337-344.
Ma, Z., Otsuyama, K., Liu, S., Abroun, S., Ishikawa, H., Tsuyama, N., Obata, M., Li, F.J., Zheng, X., Maki, Y., et al. (2005). Baicalein, a component of Scutellaria radix from Huang-Lian-Jie-Du-Tang (HLJDT), leads to suppression of proliferation and induction of apoptosis in human myeloma cells. Blood 105, 3312-3318.
Mahller, Y.Y., Williams, J.P., Baird, W.H., Mitton, B., Grossheim, J., Saeki, Y., Cancelas, J.A., Ratner, N., and Cripe, T.P. (2009). Neuroblastoma cell lines contain pluripotent tumor initiating cells that are susceptible to a targeted oncolytic virus. PLoS One 4, e4235.
Maitland, N.J., and Collins, A.T. (2008). Prostate cancer stem cells: a new target for therapy. J Clin Oncol 26, 2862-2870.
Mersereau, J.E., Levy, N., Staub, R.E., Baggett, S., Zogovic, T., Chow, S., Ricke, W.A., Tagliaferri, M., Cohen, I., Bjeldanes, L.F., et al. (2008). Liquiritigenin is a plant-derived highly selective estrogen receptor beta agonist. Mol Cell Endocrinol 283, 49-57.
Mitani, N., Murakami, K., Yamaura, T., Ikeda, T., and Saiki, I. (2001). Inhibitory effect of berberine on the mediastinal lymph node metastasis produced by orthotopic implantation of Lewis lung carcinoma. Cancer Lett 165, 35-42.
Moritsugu, K.P. (2007). The 2006 Report of the Surgeon General: the health consequences of involuntary exposure to tobacco smoke. Am J Prev Med 32, 542-543.
Mu, R., Qi, Q., Gu, H., Wang, J., Yang, Y., Rong, J., Liu, W., Lu, N., You, Q., and Guo, Q. (2009). Involvement of p53 in oroxylin A-induced apoptosis in cancer cells. Mol Carcinog 48, 1159-1169.
Murray, A.W. (2004). Recycling the cell cycle: cyclins revisited. Cell 116, 221-234.
Nuntanakorn, P., Jiang, B., Einbond, L.S., Yang, H., Kronenberg, F., Weinstein, I.B., and Kennelly, E.J. (2006). Polyphenolic constituents of Actaea racemosa. J Nat Prod 69, 314-318.
O'Brien, C.A., Pollett, A., Gallinger, S., and Dick, J.E. (2007). A human colon cancer cell capable of initiating tumour growth in immunodeficient mice. Nature 445, 106-110.
O'Reilly, K.M., McLaughlin, A.M., Beckett, W.S., and Sime, P.J. (2007). Asbestos-related lung disease. Am Fam Physician 75, 683-688.
Ong, E.S., Len, S.M., and Lee, A.C. (2005). Differential protein expression of the inhibitory effects of a standardized extract from Scutellariae radix in liver cancer cell lines using liquid chromatography and tandem mass spectrometry. J Agric Food Chem 53, 8-16.
Parada-Turska, J., Paduch, R., Majdan, M., Kandefer-Szerszen, M., and Rzeski, W. (2007). Antiproliferative activity of parthenolide against three human cancer cell lines and human umbilical vein endothelial cells. Pharmacol Rep 59, 233-237.
Park, T.Y., Park, M.H., Shin, W.C., Rhee, M.H., Seo, D.W., Cho, J.Y., and Kim, H.M. (2008). Anti-metastatic potential of ginsenoside Rp1, a novel ginsenoside derivative. Biol Pharm Bull 31, 1802-1805.
Peng, C.H., Huang, C.N., Hsu, S.P., and Wang, C.J. (2007). Penta-acetyl geniposide-induced apoptosis involving transcription of NGF/p75 via MAPK-mediated AP-1 activation in C6 glioma cells. Toxicology 238, 130-139.
Peng, C.H., Tseng, T.H., Huang, C.N., Hsu, S.P., and Wang, C.J. (2005). Apoptosis induced by penta-acetyl geniposide in C6 glioma cells is associated with JNK activation and Fas ligand induction. Toxicol Appl Pharmacol 202, 172-179.
Peng, C.H., Tseng, T.H., Liu, J.Y., Hsieh, Y.H., Huang, C.N., Hsu, S.P., and Wang, C.J. (2004). Penta-acetyl geniposide-induced C6 glioma cell apoptosis was associated with the activation of protein kinase C-delta. Chem Biol Interact 147, 287-296.
Prince, M.E., Sivanandan, R., Kaczorowski, A., Wolf, G.T., Kaplan, M.J., Dalerba, P., Weissman, I.L., Clarke, M.F., and Ailles, L.E. (2007). Identification of a subpopulation of cells with cancer stem cell properties in head and neck squamous cell carcinoma. Proc Natl Acad Sci U S A 104, 973-978.
Scheck, A.C., Perry, K., Hank, N.C., and Clark, W.D. (2006). Anticancer activity of extracts derived from the mature roots of Scutellaria baicalensis on human malignant brain tumor cells. BMC Complement Altern Med 6, 27.
Seigel, G.M., Campbell, L.M., Narayan, M., and Gonzalez-Fernandez, F. (2005). Cancer stem cell characteristics in retinoblastoma. Mol Vis 11, 729-737.
Seon, M.R., Lim, S.S., Choi, H.J., Park, S.Y., Cho, H.J., Kim, J.K., Kim, J., Kwon, D.Y., and Park, J.H. (2010). Isoangustone A present in hexane/ethanol extract of Glycyrrhiza uralensis induces apoptosis in DU145 human prostate cancer cells via the activation of DR4 and intrinsic apoptosis pathway. Mol Nutr Food Res.
Singh, S.K., Hawkins, C., Clarke, I.D., Squire, J.A., Bayani, J., Hide, T., Henkelman, R.M., Cusimano, M.D., and Dirks, P.B. (2004). Identification of human brain tumour initiating cells. Nature 432, 396-401.
Sopori, M. (2002). Effects of cigarette smoke on the immune system. Nat Rev Immunol 2, 372-377.
Takahashi, T., Takasuka, N., Iigo, M., Baba, M., Nishino, H., Tsuda, H., and Okuyama, T. (2004). Isoliquiritigenin, a flavonoid from licorice, reduces prostaglandin E2 and nitric oxide, causes apoptosis, and suppresses aberrant crypt foci development. Cancer Sci 95, 448-453.
Takara, K., Horibe, S., Obata, Y., Yoshikawa, E., Ohnishi, N., and Yokoyama, T. (2005). Effects of 19 herbal extracts on the sensitivity to paclitaxel or 5-fluorouracil in HeLa cells. Biol Pharm Bull 28, 138-142.
Tirino, V., Desiderio, V., d'Aquino, R., De Francesco, F., Pirozzi, G., Graziano, A., Galderisi, U., Cavaliere, C., De Rosa, A., Papaccio, G., et al. (2008). Detection and characterization of CD133+ cancer stem cells in human solid tumours. PLoS One 3, e3469.
Tischer, E., Mitchell, R., Hartman, T., Silva, M., Gospodarowicz, D., Fiddes, J.C., and Abraham, J.A. (1991). The human gene for vascular endothelial growth factor. Multiple protein forms are encoded through alternative exon splicing. J Biol Chem 266, 11947-11954.
Travis, W.D. (2002). Pathology of lung cancer. Clin Chest Med 23, 65-81, viii.
Travis, W.D., Travis, L.B., and Devesa, S.S. (1995). Lung cancer. Cancer 75, 191-202.
Tsai, N.M., Chen, Y.L., Lee, C.C., Lin, P.C., Cheng, Y.L., Chang, W.L., Lin, S.Z., and Harn, H.J. (2006). The natural compound n-butylidenephthalide derived from Angelica sinensis inhibits malignant brain tumor growth in vitro and in vivo. J Neurochem 99, 1251-1262.
Tsuneki, H., Ma, E.L., Kobayashi, S., Sekizaki, N., Maekawa, K., Sasaoka, T., Wang, M.W., and Kimura, I. (2005). Antiangiogenic activity of beta-eudesmol in vitro and in vivo. Eur J Pharmacol 512, 105-115.
Wakeling, A.E., Guy, S.P., Woodburn, J.R., Ashton, S.E., Curry, B.J., Barker, A.J., and Gibson, K.H. (2002). ZD1839 (Iressa): an orally active inhibitor of epidermal growth factor signaling with potential for cancer therapy. Cancer Res 62, 5749-5754.
Wang, J., Guo, L.P., Chen, L.Z., Zeng, Y.X., and Lu, S.H. (2007). Identification of cancer stem cell-like side population cells in human nasopharyngeal carcinoma cell line. Cancer Res 67, 3716-3724.
Wei, C.W., Lin, C.C., Yu, Y.L., Lin, C.Y., Lin, P.C., Wu, M.T., Chen, C.J., Chang, W., Lin, S.Z., Chen, Y.L., et al. (2009). n-Butylidenephthalide induced apoptosis in the A549 human lung adenocarcinoma cell line by coupled down-regulation of AP-2alpha and telomerase activity. Acta Pharmacol Sin 30, 1297-1306.
WHO. (February, 2009.). Cancer. (World Health Organization.).
Yang, J.G., Shen, Y.H., Hong, Y., Jin, F.H., Zhao, S.H., Wang, M.C., Shi, X.J., and Fang, X.X. (2008). Stir-baked Fructus gardeniae (L.) extracts inhibit matrix metalloproteinases and alter cell morphology. J Ethnopharmacol 117, 285-289.
Ye, F., Che, Y., McMillen, E., Gorski, J., Brodman, D., Saw, D., Jiang, B., and Zhang, D.Y. (2009). The effect of Scutellaria baicalensis on the signaling network in hepatocellular carcinoma cells. Nutr Cancer 61, 530-537.
Yuan, A., Yu, C.J., Kuo, S.H., Chen, W.J., Lin, F.Y., Luh, K.T., Yang, P.C., and Lee, Y.C. (2001). Vascular endothelial growth factor 189 mRNA isoform expression specifically correlates with tumor angiogenesis, patient survival, and postoperative relapse in non-small-cell lung cancer. J Clin Oncol 19, 432-441.
Zhang, S., Balch, C., Chan, M.W., Lai, H.C., Matei, D., Schilder, J.M., Yan, P.S., Huang, T.H., and Nephew, K.P. (2008). Identification and characterization of ovarian cancer-initiating cells from primary human tumors. Cancer Res 68, 4311-4320.
Zhang, W.D., Zhao, H.R., Yan, Y., Wang, X.H., Zong, Z.H., and Liu, Y. (2005). [Apoptosis induced by cantharidin in human pulmonary carcinoma cells A549 and its molecular mechanisms]. Zhonghua Zhong Liu Za Zhi 27, 330-334.
Zheng, H., Abdel Aziz, H.O., Nakanishi, Y., Masuda, S., Saito, H., Tsuneyama, K., and Takano, Y. (2007). Oncogenic role of JC virus in lung cancer. J Pathol 212, 306-315.
Zhuang, S.R., Chen, S.L., Tsai, J.H., Huang, C.C., Wu, T.C., Liu, W.S., Tseng, H.C., Lee, H.S., Huang, M.C., Shane, G.T., et al. (2009). Effect of citronellol and the Chinese medical herb complex on cellular immunity of cancer patients receiving chemotherapy/radiotherapy. Phytother Res 23, 785-790.
Zierau, O., Bodinet, C., Kolba, S., Wulf, M., and Vollmer, G. (2002). Antiestrogenic activities of Cimicifuga racemosa extracts. J Steroid Biochem Mol Biol 80, 125-130.