JCT  Vol.3 No.1 , February 2012
Up-Regulation of the Gap Junction Intercellular Communication by Tea Polyphenol in the Human Metastatie Lung Carcinoma Cell Line
ABSTRACT
Our previous study has proven that tea polyphenol has a role in lung neoplasms. The present communication was to investage the anti-proliferation effect of tea polyphenol on the PG cells, which was a high metastatic human lung carcinoma cell line, by 3-(4,5)-dimethylthiahiazo(-z-y1)-3,5-diphenytetrazoliumromide (MTT) cell viability assay, and to study the change of intracellular calcium concentration, connexin43 (Cx43) expression, gap junctional intercellular communication (GJIC) and cell cycle distribution after the tea polyphenol treatment by laser scanning confocal microscopy and flow cytometry. The results showed that 1) tea polyphenol could kill the PG cells in a dose-depent manner via inhibiting the PG cell proliferation and blocking the PG cell cycle progression staying in G0/G1 phase and not transfering in S and G2/M phases to reduce the PG cell proliferation index; 2) the increases of intracellular calcium concentration, GJIC and Cx43 expression were related with the tea polyphenol doses. The data suggested that tea polyphenol could inhibit the growth of PG cells, which mechanism was associated with the up-regulation of GJIC.

Cite this paper
X. Li, Q. Wang, J. Yang, Y. Pan, Q. Chen, X. Yan, D. Wang, X. Zhou and Y. Wu, "Up-Regulation of the Gap Junction Intercellular Communication by Tea Polyphenol in the Human Metastatie Lung Carcinoma Cell Line," Journal of Cancer Therapy, Vol. 3 No. 1, 2012, pp. 64-70. doi: 10.4236/jct.2012.31009.
References
[1]   H. Bartels, H.-J. Oestern and G. Voss-Wermbter, “Communicating-Occluding Junction Complexes in the Alveolar Epithelium,” American Reviews of Respiratory Disease, Vol. 21, 1980, pp. 1017-1024.

[2]   W. R. Loewenstein and Y. Kanno, “Intercellular Communication and Tissue Growth,” Journal of Cell Biology, Vol. 33, No. 2, 1967, pp. 225-234. doi:10.1083/jcb.33.2.225

[3]   J. C. Herve, N. Bourmeyster, D. Sarrouilhe and H. S. Duffy, “Gap Junctional Complexes: From Partners to Functions,” Progress in Biophysics and Molecular Biology, Vol. 94, No. 1-2, 2007, pp. 29-65. doi:10.1016/j.pbiomolbio.2007.03.010

[4]   W. R. Loewenstein, “Junctional Intercellular Communication and the Control of Growth,” Biochimica et Biophysica Acta, Vol. 560, No. 1, 1979, pp. 1-65.

[5]   C. C. Naus, “Gap Junctions and Tumour Progression,” Canadian Journal of Physiology and Pharmacology, Vol. 80, No. 2, 2002, pp. 136-141. doi:10.1139/y02-009

[6]   M. Mesnil, S. Crespin, J. L. Avanzo and M. L. Zaidan-Dagli, “Defective Gap Junctional Intercellular Communication in the Carcinogenic Process,” Biochimica et Biophysica Acta, Vol. 1719, No. 1-2, 2005, pp.125-145. doi:10.1016/j.bbamem.2005.11.004

[7]   P. R. Brink, K. Cronin, K. Banach K, E. Peterson, E. M. Westphale, K. H. Seul, S. V. Ramanan and E. C. Beyer, “Evidence for HEteromeric Gap Junction Channels Formed Rat Connexin43 and Human Connexin37,” American Journal of Physiology, Vol. 274, No. 4, 1997, pp. 1386-1392.

[8]   C. Borek, S. Higashino and W. R. Loewenstein, “Intercellular Communication and Tissue growth IV. Conductance of Membrane Junctions of Normal and Cancerous Cells in Culture,” Journal of Membrane Biology, Vol. 1, No. 1, 1969, pp. 274-293. doi:10.1007/BF01869786

[9]   Y. Kanno and Y. Matsui, “Cellular Uncoupling in Cancerous Stomach Epithelium,” Nature, Vol. 218, No. 5143, 1968, pp. 775-776. doi:10.1038/218775b0

[10]   W. R. Loewenstein and Y. Kanno, “Intercellular Communication and the Control of Tissue Growth: Lack of Communication between Cancer Cells,” Nature, Vol. 209, No. 5029, 1966, pp. 1248-1249. doi:10.1038/2091248a0

[11]   M. Mesnil, R. Montesano and H. Yamasaki, “Intercellular Communication of Transformed and Non-Transformed Rat Liver Epithelial Cells,” Experimental Cell Research, Vol. 165, No. 2, 1986, pp. 391-402. doi:10.1016/0014-4827(86)90593-8

[12]   D. A. Goodenough, J. A. Goliger and D. L. Paul, “Connexins, Connexons and Intercellular Communication,” Annual Reviews Biochemistry, Vol. 65, No. 1, 1996, pp. 475-502. doi:10.1146/annurev.bi.65.070196.002355

[13]   A. M. Simon and D. A. Goodenough, “Diverse Functions of Vertebrate Gap Junctions,” Trends Cell Biology, Vol. 8, No. 12, 1998, pp. 477-483. doi:10.1016/S0962-8924(98)01372-5

[14]   E. C. Beyer, J. Kistler, D. L. Paul and D. A. Goodenough, “Antisera Directed against Connexin43 Peptides React with a 43-kDa Protein Localized to Gap Junctions in Myometrium and Other Tissues,” Journal of Cell Biology, Vol. 108, No. 2, 1989, pp. 595-605. doi:10.1083/jcb.108.2.595

[15]   R. J. Ruch, “The Role of Gap Junction Intercellular Communication in Neoplasia,” Annals of Clinical and Laboratory Sciences, Vol. 24, No. 3, 1994, pp. 216-231.

[16]   H. Tsai, J. Werber, M. O. Davia, M. Edelman, K. M. Tanaka, A. Melman, G. J. Christ and J. Geliebter, “Reduced Connexin43 Expression in High Grade, Human Prostatic Adenocarcinoma Cells,” Biochemical and Biophysical Research Communications, Vol. 229, No. 1, 1996, pp. 64-69. doi:10.1006/bbrc.1996.1468

[17]   K. K. Hirschi, C. E. Xu, T. Tsukamoto and R. Sager, “Gap Junction Genes Cx26 and Cx43 Individually Suppress the Cancer Phenotype of Human Mammary Carcinoma Cells and Restore Differentiation Potential,” Cell Growth & Differentiation, Vol. 7, No. 7, 1996, pp. 861-870.

[18]   D. W. Laird, P. Fistouris, G. Batist, L. Alpert, H. T. Huynh, G. D. Carystions and M. A. Alaoui-Jamali, “Deficiency of Connexin43 Gap Junctions Is an Independent Marker for Breast Tumors,” Cancer Research, Vol. 59, No. 16, 1999, pp. 4104-4110.

[19]   R. J. Ruch, K. Cesen-Cummings and A. Malkinson, “Role of Gap Junctions in Lung Neoplasia,” Experimental Lung Research, Vol. 24, No. 4, 1998, pp.523-539. doi:10.3109/01902149809087384

[20]   R. P. Huang, M. Z. Hossain, A. Sehgal and A. L. Boynton, “Reduced Connexin43 Expression in High-Grade Human Brain Glioma Cells,” Journal of Surgical Oncology, Vol. 70, No. 1, 1999, pp. 21-24. doi:10.1002/(SICI)1096-9098(199901)70:1<21::AID-JSO4>3.0.CO;2-0

[21]   K. Willecke, J. Eiberger, J. Degen, D. Eckardt, A. Romualdi, M. Guldenagel and G. Sohl, “Structural and Functional Diversity of Connexin Genes in the Mouse and Human Genome,” Biological Chemistry, Vol. 383, No. 5, 2002, pp. 725-737. doi:10.1515/BC.2002.076

[22]   A. Okuma, A. Kuraoka, H. Iida, T. Inai, K. Wasano and Y. Shibata, “Colocalization of Connexin 43 and connexin 45 but Absence of Connexin 40 in Granulosa Cell Gap Junctions of Rat Ovary,” The Journal of the Society for Reproduction and Fertility, Vol. 107, No. 2, 1996, pp. 255-264. doi:10.1530/jrf.0.1070255

[23]   M. S. Risley, I. P. Tan, C. Roy and J. C. Saez, “Cell-, Age- and Stagedependent Distribution of Connexin43 Gap Junctions in Testes,” Journal of Cell Science, Vol. 103, No. 1, 1992, pp. 81-96.

[24]   Y. Kato, T. Hirano, K. Yoshida, K. Yashima, S. Akimoto, K. Tsuji, T. Ohira, M. Tsubol, N. Ikeda, Y. Ebihara and H. Kato, “Frequent Loss of E-Cadherin and/or Catenins in Intrabronchial Lesions during Carcinogenesis of the Bronchial Epithelium,” Lung Cancer, Vol. 48, No. 3, 2005, pp. 323-330. doi:10.1016/j.lungcan.2004.11.012

[25]   J. T. Chen, Y. W. Cheng, M. C. Chou, T. Sen-Lin, W. W. Lai, W. L. Ho and H. Lee, “The Correlation between Aberrant Connexin 43 mRNA Expression Induced by Promoter Methylation and Nodal Micrometastasis in Non-Small Cell Lung Cancer,” Clinical Cancer Reserch, Vol. 9, No. 11, 2003, pp. 4200-4204.

[26]   R. Brehm, C. Rüttinger, P. Fischer, I. Gashaw, E. Winterhager, S. Kliesch, R. M. Bohle, K. Steger and M. Bergmann, “Transition from Preinvasive Carcinoma in Situ to Seminoma Is Accompanied by a Reduction of Connexin 43 Expression in Sertoli Cells and Germ Cells,” Neoplasia, Vol. 8, No. 6, 2006, pp. 499-509. doi:10.1593/neo.05847

[27]   Z. Q. Zhang, Z. X. Lin and Y. L. Han, “Expression of Gap Junction Protein Cx43 in Cultured Normal Human Ernbryonic Lung Cells and Lung Carcinoma Cells,” Acta Biophysics Sinica (in Chinese), Vol. 4, 1994, pp. 411-413.

[28]   J. I. Morgan and T. Curran, “Role of Ion Flux in the Control of c-fos Expression,” Nature, Vol. 322, No. 6079, 1986, pp. 552-555. doi:10.1038/322552a0

[29]   D. Carson and J. Ribeiro, “Apoptosis and Disease,” Lancet, Vol. 341, No. 8855, 1993, pp. 1251-1258. doi:10.1016/0140-6736(93)91154-E

[30]   W. M. Jongen, D. J. Fitzgerald, M. Asamoto, C. Piccoli, T. J. Slaga, D. Gros, M. Takeichi and H. Yamasaki, “Regulation of Connexin43-Mediated Gap Junctional Intercellular Communication by Ca2+ in Mouse Epidermal Cells is Controlled by E-Cadherin,” Journal of Cell Biology, Vol. 144, No. 3, 1991, pp. 545-555. doi:10.1083/jcb.114.3.545

[31]   C. S. Yang and Z. Y. Wang, “Tea and Cancer,” Journal of the National Cancer Institute, Vol. 85, No. 3, 1993, pp. 1038-1049. doi:10.1093/jnci/85.13.1038

[32]   C. S. Yang, P. Maliakal and X. Meng, “Inhibition of Carcinogenesis by Tea,” Annual Reviews Pharmacology and Toxicology, Vol. 42, No. 1, 2002, pp. 25-54. doi:10.1146/annurev.pharmtox.42.082101.154309

[33]   J. Ju, G. Lu, J. D. Lambert and C. S. Yang, “Inhibition of Carcinogenesis by Tea Constituents,” Seminars in Cancer Biology, Vol. 17, No. 5, 2007, pp. 395-402. doi:10.1016/j.semcancer.2007.06.013

[34]   C. S. Yang, X. Wang, G. Lu and S. C. Picinich, “Cancer Prevention by Tea: Animal Studies, Molecular Mechanisms and Human Relevance,” National Reviews Cancer, Vol. 9, No. 6, 2009, pp. 429-439. doi:10.1038/nrc2641

[35]   J. V. Higdon and B. Frei, “Tea Catechins and Polyphenols: Health Effects, Metabolism, and Antioxidant Functions,” Critical Reviews in Food Science and Nutrition, Vol. 43, No. 1, 2003, pp. 89-143. doi:10.1080/10408690390826464

[36]   V. Crespy and G. Williamson, “A Review of the Health Effects of Green Tea Catechins in Vivo Animal Models,” The Journal of Nutrition, Vol. 134, No. 12, 2004, pp. 3431S-3440S.

[37]   J. Y. Ju, G. Lu, D. J. Lambert and C. S. Yang, “Inhibition of Carcinogenesis by Tea Constituents,” Seminars in Cancer Biology, Vol. 17, No. 5, 2007, pp. 395-402. doi:10.1016/j.semcancer.2007.06.013

[38]   H. Mukhtar, S. K. Katiyar and R. Agarwal, “Green Tea and Skin—Anticarcinogenic Effects,” Journal of Investigative Dermatology, Vol. 102, No. 1, 1994, pp. 3-7. doi:10.1111/1523-1747.ep12371720

[39]   I. E. Dreosti, M. J. Wargovich and C. S. Yang, “Inhibition of Carcinogenesis by Tea: The Evidence from Experimental Studies,” Critical Reviews in Food Science and Nutrition, Vol. 37, No. 8, 1997, pp. 761-770. doi:10.1080/10408399709527801

[40]   F. L. Chung, J. Schwartz, C. R. Herzog and Y. M. Yang, “Tea and Cancer Prevention: Studies in Animals and Humans,” The Journal of Nutrition, Vol. 133, No. 10, 2003, pp. 3268S-3274S.

[41]   J. D. Lambert, J. Hong, G. Y. Yang, J. Liao and C. S. Yang, “Inhibition of Carcinogenesis by Polyphenols: Evidence from Laboratory Investigations,” The American Journal of Clinical Nutrition, Vol. 81, No. 1, 2005, pp. 284S-291S.

[42]   D. M. Parkin, “Global Cancer Statistics in the Year 2000,” Lancet Oncology, Vol. 2, No. 9, 2001, pp. 533-543. doi:10.1016/S1470-2045(01)00486-7

[43]   D. M. Parkin, F. Bray, J. Ferlay and P. Pisani, “Global Cancer Statistics, 2002,” CA: A Cancer Journal of Clinicians, Vol. 55, No. 2, 2005, pp. 74-108. doi:10.3322/canjclin.55.2.74

[44]   S. Valcic, B. N. Timmermann, D. S. Alberts, G. A. Wachter, M. Krutzsch, J. Wymer and J.M. Guillen, “Inhibitory Effect of Six Green Tea Catechins and Caffeine on the Growth of Four Selected Human Tumor Cell Lines,” Anti-Cancer Drugs, Vol. 7, No. 4, 1996, pp. 461-468. doi:10.1097/00001813-199606000-00011

[45]   S. Okabe, M. Suganuma, M. Hayashi, E. Sueoka, A. Komori and H. Fujiki, “Mechanisms of Growth Inhibition of Human Lung Cancer Cell Line, PC-9, by Tea Polyphenols,” Cancer Science, Vol. 88, No. 7, 1997, pp. 639-643. doi:10.1111/j.1349-7006.1997.tb00431.x

[46]   C. S. Yang, J. Liao, G. Y. Yang and G. Lu, “Inhibition of Lung Tumorigenesis by Tea,” Experimental Lung Research, Vol. 31, No. 1, 2005, pp. 135-144. doi:10.1080/01902140490495525

[47]   T. Kuzuhara, A. Tanabe, Y. Sei, K. Yamaguchi, M. Suganuma and H. Fujiki, “Synergistic Effects of Multiple Treatments, and both DNA and RNA Direct Bindings on, Green Tea Catechins,” Molecular Carcinogenesis, Vol. 46, No. 8, 2007, pp. 640-645. doi:10.1002/mc.20332

[48]   D. Sadava, E. Whitlock and S. E. Kane, “The Green Tea Polyphenol, Epigallocatechin-3-gallate Inhibits Telomerase and Induces Apoptosis in Drug-Resistant Lung Cancer Cells,” Biochemical and Biophysical Research Communications, Vol. 360, No. 1, 2007, pp. 233-237. doi:10.1016/j.bbrc.2007.06.030

[49]   C. Q. Yong, Y. Q. Wu, Y. Q. Jiang and X. Xiao, “Adhesion Molecules in the Blood of Lung Cancer Metastasis and the Role of Polyphenols in the Regulation,” Journal of Military Medicine, Vol. 27, No. 4, No. , 2002, pp. 339-344.

[50]   H. Yamasaki, M. Mesnil, Y. Omori, N. Mironov and V. Krutovskikh, “Intercellular Communication and Carcinogenesis,” Mutation Research, Vol. 333, No. 1-2, 1995, pp. 181-188. doi:10.1016/0027-5107(95)00144-1

[51]   E. Tomai, H. Brownell, T. Tufescu, K. Reid, B. G. Campling and L. Raptis, “Gap Junctional Intercellular Communication in Cultured Human Lung Carcinoma Cells,” Lung Cancer, Vol. 23, No. 3, 1999, pp. 223-231. doi:10.1016/S0169-5002(99)00016-1

[52]   P. Pu, Z. Xia, S. Yu and Q. Huang, “Altered Expression of Cx43 in Astrocytic Tumors,” Clinical Neurology and Neurosurgery, Vol. 107, No. 1, 2004, pp. 49-54. doi:10.1016/j.clineuro.2004.03.006

[53]   L. Soroceanu, T. J. Manning Jr. and H. Sontheimer, “Reduced Expression of Connexin-43 and Functional Gap Junction Coupling in Human Gliomas,” Glia, Vol. 33, No. 2, 2001, pp. 107-117. doi:10.1002/1098-1136(200102)33:2<107::AID-GLIA1010>3.0.CO;2-4

[54]   D. Laird, P. Fisturis, G. Batist, L. Alpert, H. T. Huynh, G. D. Carystinos and M. A. Alaoui-Jamali, “Deficiency of Connexin 43 Gap Junctions Is an Independent Marker for Breast Tumors,” Cancer Research, Vol. 59, No. 16, 1999, pp. 4104-4110.

[55]   O. Traub, R. Eckert, H. Lichtenberg-Frate, C. Elfgang, B. Bastide, K. H. Scheidtmann, D. F. Hülser and K. Willecke, “Immunochemical and Electrophysiological Characterization of Murine Connexin40 and 43 in Mouse Tissues and Transfected Human Cells,” European Journal of Cell Biology, Vol. 64, No. 1, 1994, pp. 101-112.

[56]   J. E. Trosko and R. J. Ruch, “The Role of Cell-Cell Communication in Carcinogenesis,” Frontiers in Bioscience, Vol. 3, 1998, pp. 208-236.

[57]   R. W. Banoub, M. Fernstrom, A. M. Malkinson and R. J. Ruch, “Enhancement of Gap Junctional by Dibutyryl Cyclic AMP in Lung Epithelial Cells,” Anti-Cancer Research, Vol. 16, No. 6B, 1996, pp. 3715-3719.

[58]   T. Toyofuku, M. Yabuki, K. Otsu, T. Kuzuya, M. Hori and M. Tada, “Intercellular Calcium Signaling via Gap Junction in Connexin 43 Transfected Cells,” Journal of Biological Chemistry, Vol. 273, No. 3, 1998, pp. 1519-1528. doi:10.1074/jbc.273.3.1519

[59]   Q. Shao, H. Wang, E. McLachlan, G. I. Veitch and D. W. Laird, “Down-Regulation of Cx43 by Retroviral Delivery of Small Interfering RNA Promotes an Aggressive Breast Cancer Cell Phenotype,” Cancer Research, Vol. 65, No. 7, 2005, pp. 2705-2711. doi:10.1158/0008-5472.CAN-04-2367

[60]   X. Xu, R. Francis, C. J. Wei, K. L. Linask and C. W. Lo, “Connexin 43-Mediated Modulation of Polarized Cell Movement and the Directional Migration of Cardiac Neural Crest Cells,” Development, Vol. 133, No. 18, 2006, pp. 3629-3639. doi:10.1242/dev.02543

[61]   J. H. Lin, T. Takano, M. L. Cotrina, G. Arcuino, J. Kang, S. Liu, Q. Gao, L. Jiang, F. Li, H. Lichtenberg-Frate, S. Haubrich, K. Willecke, S. A. Goldman and M. Nedergaard, “Connexin 43 Enhances the Adhesivity and Mediates the Invasion of Malignant Glioma Cells,” Journal of Neuroscience, Vol. 22, No. 11, 2002, pp. 4302-4311.

[62]   R. Oliveira, C. Christov, J. S. Guillamo, S. de Bouard, S. Palfi, L. Venance, M. Tardy and M. Peschanski, “Contribution of Gap Junctional Communication between Tumor Cells and Astroglia to the Invasion of the Brain Parenchyma by Human Glioblastomas,” BMC Cell Biology, Vol. 6, No. 1, 2005, pp. 7-21. doi:10.1186/1471-2121-6-7

[63]   W. Zhang, C. Nwagwu, D. M. Le, V. W. Yong, H. Song and W. T. Couldwell, “Increased Invasive Capacity of Connexin43-Overexpressing Malignant Glioma Cells,” Journal of Neurosurgery, Vol. 99, No. 6, 2003, pp. 1039-1046. doi:10.3171/jns.2003.99.6.1039

[64]   L. A. Elias, D. D. Wang and A. R. Kriegstein, “Gap Junction Adhesion Is Necessary for Radial Migration in the Neocortex,” Nature, Vol. 448, No. 7156, 2007, pp. 901-907. doi:10.1038/nature06063

[65]   C. Cina, K. Maass, M. Theis, K. Willecke, J. F. Bechberger and C. C. Naus, “Involvement of the Cytoplasmic C-Terminal Domain of Connexin43 in Neuronal Migration,” Journal of Neuroscience, Vol. 29, No. 7, 2009, pp. 2009-2021. doi:10.1523/JNEUROSCI.5025-08.2009

[66]   Y. W. Zhang, M. Kaneda and I. Morita, “The Gap Junction-Independent Tumor-Suppressing Effect of Connexin 43,” Journal of Biological Chemistry, Vol. 278, No. 45, 2003, pp. 44852-44856. doi:10.1074/jbc.M305072200

[67]   D. C. Bates, W. C. Sin, Q. Aftab and C. C. Naus, “Connexin43 Enhances Glioma Invasion by a Mechanism Involving the Carboxy Terminus,” Glia, Vol. 55, No. 15, 2007, pp. 1554-1564. doi:10.1002/glia.20569

[68]   W. C. Sin, S. Crespin and M. Mesnil, “Opposing Roles of Connexin43 in Glioma Progression,” Biochimica et Biophysica Acta, Vol. 10, No. 4C, 2011, pp. 4-6.

 
 
Top