Apigenin inhibits growth and motility but increases gap junctional coupling intensity in rat prostate carcinoma [MAT-LyLu] cell populations

• Autorzy: Czernik M , Sroka J. , Madeja Z. , Czyz J.
• Języki publikacji: EN

Abstrakty

EN

Apigenin (4′,5,7,-trihydroxyflavone) is a flavonoid abundant in the common fruits, herbs and vegetables constituting the bulk of the human diet. This study was aimed at quantifying the effects of apigenin on the basic cellular traits determining cancer development, i.e. cell proliferation, gap junctional coupling, and motility, using the Dunning rat prostate MAT-LyLu cell model. We demonstrated that apigenin considerably inhibits MAT-LyLu cell proliferation and significantly enhances the intensity of connexin43-mediated gap junctional coupling. This effect correlates with an increased abundance of C×43-positive plaques at the cell-to-cell borders seen in apigenin-treated variants. Moreover, we observed an inhibitory effect of apigenin on the motility of MAT-LyLu cells. The basic parameters characterising MAT-LyLu cell motility, especially the rate of cell displacement, considerably decreased upon apigenin administration. This in vitro data indicates that apigenin may affect cancer development in general, and prostate carcinogenesis in particular, via its influence on cellular activities decisive for both cancer promotion and progression, including cell proliferation, gap junctional coupling and cell motility and invasiveness.

Słowa kluczowe

EN

prostate cancer; rat; cell motility; gap junctional coupling; apigenin; carcinoma; cell population; MAT-LyLu cell; cancer development

• Wydawca: -
• Czasopismo: Cellular and Molecular Biology Letters
• Rocznik: 2008
• Tom: 13
• Numer: 3
• Strony: 327-338
• Opis fizyczny: p.327-338,fig.,ref.

Twórcy

autor

Czernik M

• Jagiellonian University, Gronostajowa 7, 30-387 Krakow, Poland

autor

Sroka J.

autor

Madeja Z.

autor

Czyz J.

Bibliografia

• 1. Yamasaki, H., Krutovskikh, V., Mesnil, M., Tanaka, T., Zaidan-Dagli, M.L. and Omori, Y. Role of connexin (gap junction) genes in cell growth control and carcinogenesis. C. R. Acad. Sci. III 322 (1999) 151-159.
• 2. Zhang, Y.W., Kaneda, M. and Morita, I. The gap junction-independent tumor-suppressing effect of connexin 43. J. Biol. Chem. 278 (2003) 44852- 44856.
• 3. Guo, W. and Giancotti, F.G. Integrin signalling during tumour progression. Nat. Rev. Mol. Cell Biol. 5 (2004) 816-826.
• 4. Gupta, G.P. and Massague, J. Cancer metastasis: building a framework. Cell 127 (2006) 679-695.
• 5. Yamaguchi, H., Wyckoff, J. and Condeelis, J. Cell migration in tumors. Curr. Opin. Cell Biol. 17 (2005) 559-564.
• 6. Chambers, A.F. The metastatic process: basic research and clinical implications. Oncol. Res. 11 (1999) 161-168.
• 7. Czyż, J. Stage-Specific Function of gap junctions during tumorigenesis. Cell. Mol. Biol. Lett. 13 (2008) 92-102.
• 8. Lambert, J.D., Hong, J., Yang, G.Y., Liao, J. and Yang, C.S. Inhibition of carcinogenesis by polyphenols: evidence from laboratory investigations. Am. J. Clin. Nutr. 81 (2005) 284S-291S.
• 9. Sarkar, F.H. and Li, Y. The role of isoflavones in cancer chemoprevention. Front Biosci. 9 (2004) 2714-2724.
• 10. Patel, D., Shukla, S. and Gupta, S. Apigenin and cancer chemoprevention: progress, potential and promise (review). Int. J. Oncol. 30 (2007) 233-245.
• 11. Birt, D.F., Mitchell, D., Gold, B., Pour, P. and Pinch, H.C. Inhibition of ultraviolet light induced skin carcinogenesis in SKH-1 mice by apigenin, a plant flavonoid. Anticancer Res. 17 (1997) 85-91.
• 12. Lepley, D.M., Li, B., Birt, D.F. and Pelling, J.C. The chemopreventive flavonoid apigenin induces G2/M arrest in keratinocytes. Carcinogenesis 17 (1996) 2367-2375.
• 13. Lepley, D.M. and Pelling, J.C. Induction of p21/WAF1 and G1 cell-cycle arrest by the chemopreventive agent apigenin. Mol. Carcinog. 19 (1997) 74-82.
• 14. Gupta, S., Afaq, F. and Mukhtar, H. Selective growth-inhibitory, cell-cycle deregulatory and apoptotic response of apigenin in normal versus human prostate carcinoma cells. Biochem. Biophys. Res. Commun. 287 (2001) 914-920.
• 15. Shukla, S., Mishra, A., Fu, P., MacLennan, G.T., Resnick, M.I. and Gupta, S. Up-regulation of insulin-like growth factor binding protein-3 by apigenin leads to growth inhibition and apoptosis of 22Rv1 xenograft in athymic nude mice. FASEB J. 19 (2005) 2042-2044.
• 16. Ujiki, M.B., Ding, X.Z., Salabat, M.R., Bentrem, D.J., Golkar, L., Milam, B., Talamonti, M.S., Bell, R.H., Jr., Iwamura, T. and Adrian, T.E. Apigenin inhibits pancreatic cancer cell proliferation through G2/M cell cycle arrest. Mol. Cancer 5 (2006) 76.
• 17. Shukla, S. and Gupta, S. Apigenin-induced cell cycle arrest is mediated by modulation of MAPK, PI3K-Akt, and loss of cyclin D1 associated retinoblastoma dephosphorylation in human prostate cancer cells. Cell Cycle 6 (2007) 1102-1114.
• 18. Caltagirone, S., Rossi, C., Poggi, A., Ranelletti, F.O., Natali, P.G., Brunetti, M., Aiello, F.B. and Piantelli, M. Flavonoids apigenin and quercetin inhibit melanoma growth and metastatic potential. Int. J. Cancer 87 (2000) 595-600.
• 19. Czyż, J., Madeja, Z., Irmer, U., Korohoda, W. and Hulser, D.F. Flavonoid apigenin inhibits motility and invasiveness of carcinoma cells in vitro. Int. J. Cancer 114 (2005) 12-18.
• 20. Piantelli, M., Rossi, C., Iezzi, M., La Sorda, R., Iacobelli, S., Alberti, S. and Natali, P.G. Flavonoids inhibit melanoma lung metastasis by impairing tumor cells endothelium interactions. J. Cell. Physiol. 207 (2006) 23-29.
• 21. Gopalakrishnan, A., Xu, C.J., Nair, S.S., Chen, C., Hebbar, V. and Kong, A.N. Modulation of activator protein-1 (AP-1) and MAPK pathway by flavonoids in human prostate cancer PC3 cells. Arch. Pharm. Res. 29 (2006) 633-644.
• 22. Madeja, Z., Miekus, K., Sroka, J., Djamgoz, M.B. and Korohoda, W. Homotypic cell-cell contacts stimulate the motile activity of rat prostate cancer cells. BJU Int. 88 (2001) 776-786.
• 23. Miękus, K. and Madeja, Z. Genistein inhibits the contact-stimulated migration of prostate cancer cells. Cell. Mol. Biol. Lett. 12 (2007) 348-361.
• 24. Chaumontet, C., Bex, V., Gaillard-Sanchez, I., Seillan-Heberden, C., Suschetet, M. and Martel, P. Apigenin and tangeretin enhance gap junctional intercellular communication in rat liver epithelial cells. Carcinogenesis 15 (1994) 2325-2330.
• 25. Czyż, J., Irmer, U., Schulz, G., Mindermann, A. and Hulser, D.F. Gapjunctional coupling measured by flow cytometry. Exp. Cell Res. 255 (2000) 40-46.
• 26. Czyż, J., Guan, K., Zeng, Q. and Wobus, A.M. Loss of beta 1 integrin function results in upregulation of connexin expression in embryonic stem cell-derived cardiomyocytes. Int. J. Dev. Biol. 49 (2005) 33-41.
• 27. Sroka, J., Kamiński, R., Michalik, M., Madeja, Z., Przestalski, S. and Korohoda, W. The effect of triethyllead on the motile activity of walker 256 carcinosarcoma cells. Cell. Mol. Biol. Lett. 9 (2004) 15-30.
• 28. Czyż, J., Irmer, U., Zappe, C., Mauz, M. and Hulser, D.F. Hierarchy of carcinoma cell responses to apigenin: gap junctional coupling versus proliferation. Oncol. Rep. 11 (2004) 739-744.
• 29. Wang, W., Heideman, L., Chung, C.S., Pelling, J. C., Koehler, K.J. and Birt, D.F. Cell-cycle arrest at G2/M and growth inhibition by apigenin in human colon carcinoma cell lines. Mol. Carcinog. 28 (2000) 102-110.
• 30. Chaumontet, C., Droumaguet, C., Bex, V., Heberden, C., Gaillard-Sanchez, I. and Martel, P. Flavonoids (apigenin, tangeretin) counteract tumor promoter-induced inhibition of intercellular communication of rat liver epithelial cells. Cancer Lett. 114 (1997) 207-210.
• 31. Grimstad, I.A. Direct evidence that cancer cell locomotion contributes importantly to invasion. Exp. Cell Res. 173 (1987) 515-523.
• 32. Miękus, K., Czernik, M., Sroka, J., Czyż, J. and Madeja, Z. Contact stimulation of prostate cancer cell migration: the role of gap junctional coupling and migration stimulated by heterotypic cell-to-cell contacts in determination of the metastatic phenotype of dunning rat prostate cancer cells. Biol. Cell 97 (2005) 893-903.