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Differential Effect of Curcumin on the Nanomechanics of Normal and Cancerous Mammalian Epithelial Cells

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Abstract

Though the pharmacological activity of curcumin inhibiting the proliferation of certain cancer cells in culture was demonstrated, its effect on early-stage modifications induced in cell mechanics influencing hereby cell growth and cell adhesion are still questionable. We investigate the morphology and the elastic properties of live cultured, non-malignant human mammalian epithelial cells (HMEC) and cancerous breast epithelial cells (MCF7) by atomic force microscopy. We describe the different behavior of the two similar cell lines under curcumin treatment and we use fluorescence microscopy to identify the microtubules as the cytoskeleton structures responding to curcumin. The first changes in the HMEC cell morphology are observed after already 2 h incubation with curcumin. A 6-h long treatment leaves the MCF7 cells morphology non-affected, but the microtubules of HMEC cells disassemble and form a ring-like organization circumscribing the nuclear area. The observed morphological changes were correlated to modifications in cell’s mechanics via elasticity force mapping measurements. Curcumin treatment modified elasticity of the HMEC cells increasing the cell’s average Young’s modulus two- to threefold, especially in the cytoplasmic area. Contrariwise, a slight decrease in the Young’s modulus was noticed for the MCF7 cells, as they become softer due to the action of curcumin. Chemotherapeutic drugs exert their effect via the perturbation of the dynamic instability of the microtubule, hence the cell-specific perturbation induced by curcumin can help in future understanding of drug induced events on the cell behavior.

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References

  1. Lekka, M., Laidler, P., Gil, D., Lekki, J., Stachura, Z., & Hrynkiewicz, A. Z. (1999). Elasticity of normal and cancerous human bladder cells studied by scanning force microscopy. European Biophysics Journal, 28, 312–316.

    Article  PubMed  CAS  Google Scholar 

  2. Lekka, M., Lekki, J., Marszałek, M., Golonka, P., Stachura, Z., Cleff, B., et al. (1999). Local elastic properties of cells studied by SFM. Applied Surface Science, 141, 345–349.

    Article  CAS  Google Scholar 

  3. Berdyyeva, T. K., Woodworth, C. D., & Sokolov, I. (2005). Human epithelial cells increase their rigidity with ageing in vitro: Direct measurements. Physics in Medicine and Biology, 50, 81–92.

    Article  PubMed  Google Scholar 

  4. Yamazaki, D., Kurisu, S., & Takenawa, T. (2005). Regulation of cancer cell motility through actin reorganization. Cancer Science, 96, 379–386.

    Article  PubMed  CAS  Google Scholar 

  5. Rao, J., & Li, N. (2004). Microfilament actin remodeling as a potential target for cancer drug development. Current Cancer Drug Targets, 4, 267–283.

    Article  Google Scholar 

  6. Goldmann, W. H., & Ezzell, R. M. (1996). Viscoelasticity in wild-type and vinculin-deficient (5.51) mouse F9 embryonic carcinoma cells examined by atomic force microscopy and rheology. Experimental Cell Research, 1996(226), 234–237.

    Article  Google Scholar 

  7. Goldmann, W. H., Galneder, R., Ludwig, M., Xu, W. M., Adamson, E. D., Wang, N., et al. (1998). Differences in elasticity of vinculin-deficient F9 cells measured by magnetometry and atomic force microscopy. Experimental Cell Research, 239, 235–242.

    Article  PubMed  CAS  Google Scholar 

  8. Discher, D., Janmey, P., & Wang, Y. (2005). Tissue cells feel and respond to the stiffness of their substrate. Science, 310, 1139–1143.

    Article  PubMed  CAS  Google Scholar 

  9. McKnight, A. L., Kugel, J. L., Rossman, P. J., Manduca, A., Hartmann, L. C., & Ehman, R. L. (2002). MR elastography of breast cancer: Preliminary results. American Journal of Roentgenology, 178, 1411–1417.

    Article  PubMed  Google Scholar 

  10. Bercoff, J., Chaffaï, S., Tanter, M., Sandrin, L., Catheline, S., Fink, M., et al. (2003). In vivo breast tumor detection using transient elastography. Ultrasound in Medicine and Biology, 29, 1387–1396.

    Article  PubMed  CAS  Google Scholar 

  11. Rotsch, C., & Radmacher, M. (2000). Drug-induced changes of cytoskeletal structure and mechanics in fibroblasts: An atomic force microscopy study. Biophysical Journal, 78, 520–535.

    Article  PubMed  CAS  Google Scholar 

  12. Suresh, S., Spatz, J., Mills, J. P., Micoulet, A., Dao, M., Lim, C. T., et al. (2005). Connections between single-cell biomechanics and human disease states: Gastrointestinal cancer and malaria. Acta Biomaterialia, 1, 15–30.

    Article  PubMed  CAS  Google Scholar 

  13. Guck, J., Schinkinger, S., Lincoln, B., Wottawah, F., Ebert, S., Romeyke, M., et al. (2005). Optical deformability as an inherent cell marker for testing malignant transformation and metastatic competence. Biophysical Journal, 88, 3689–3698.

    Article  PubMed  CAS  Google Scholar 

  14. Suresh, S. (2007). Biomechanics and biophysics of cancer cell. Acta Biomaterialia, 3, 413–438.

    Article  PubMed  Google Scholar 

  15. Cross, S. E., Jin, Y. S., Rao, J., & Gimzewski, J. K. (2007). Nanomechanical analysis of cells from cancer patients. Nature Nanotechnology, 2, 780–783.

    Article  PubMed  CAS  Google Scholar 

  16. Binnig, G., Quate, C. F., & Gerber, C. (1986). Atomic force microscope. Physical Review Letters, 56, 930–933.

    Article  PubMed  Google Scholar 

  17. Radmacher, M., Tillamnn, R. W., Fritz, M., & Gaub, H. E. (1992). From molecules to cells: Imaging soft samples with the atomic force microscope. Science, 257, 1900–1905.

    Article  PubMed  CAS  Google Scholar 

  18. Hansma, P. K., Elings, V. B., Marti, O., & Bracker, C. E. (1988). Scanning tunneling microscopy and atomic force microscopy: Application to biology and technology. Science, 242, 209–216.

    Article  PubMed  CAS  Google Scholar 

  19. Domke, J., Danno, S., Parak, W. J., Muller, O., Aicher, W. K., & Radmacher, M. (2000). Substrate dependent differences in morphology and elasticity of living osteoblasts investigated by atomic force microscopy. Colloid Surface B., 19, 367–379.

    Article  CAS  Google Scholar 

  20. Hertz, H. (1881). Über die Berührung fester elastischer Körper. J Reine Angew Math, 92, 156–171.

    Google Scholar 

  21. Charras, G. T., & Horton, M. A. (2002). Single cell mechanotransduction and its modulation analyzed by atomic force microscopy indentation. Biophysical Journal, 2002(82), 2970–2981.

    Article  Google Scholar 

  22. Dufrene, Y. F. (2002). Atomic force microscopy, a powerful tool in microbiology. Journal of Bacteriology, 2002(184), 5205–5213.

    Article  Google Scholar 

  23. Balint, Z., Krizbai, I. A., Wilhelm, I., Farkas, A. E., Parducz, A., Szegletes, Z., et al. (2007). Changes induced by hyperosmotic mannitol in cerebral endothelial cells: An atomic force microscopic study. European Biophysics Journal, 36, 113–120.

    Article  PubMed  CAS  Google Scholar 

  24. Rotsch, C., Braet, F., Wisse, E., & Radmacher, M. (1997). AFM imaging and elasticity measurements on living rat liver macrophages. Cell Biology International, 21, 685–696.

    Article  PubMed  CAS  Google Scholar 

  25. Aggarwal, B. B., & Shishodia, S. (2006). Molecular targets of dietary agents for prevention and therapy of cancer. Biochemical Pharmacology, 2006(71), 1397–1421.

    Article  Google Scholar 

  26. Choi, H., Chun, Y. S., Kim, S. W., Kim, M. S., & Park, J. W. (2006). Curcumin inhibits hypoxia-inducible factor-1 by degrading aryl hydrocarbon receptor nuclear translocator: A mechanism of tumor growth inhibition. Molecular Pharmacology, 70, 1664–1671.

    Article  PubMed  CAS  Google Scholar 

  27. Shukla, P. K., Khanna, V. K., Ali, M. M., Khan, M. Y., & Srimal, R. (2008). CAnti-ischemic effect of curcumin in rat brain. Neurochemical Research, 33, 1036–1043.

    Article  PubMed  CAS  Google Scholar 

  28. Stix, G. (2007). Spice healer. Scientific American, 296, 66–69.

    Google Scholar 

  29. Shukla, P. K., Khanna, V. K., Khan, M. Y., & Srimal, R. C. (2003). Protective effect of curcumin against lead neurotoxicity in rat. Human and Experimental Toxicology, 22, 653–658.

    Article  PubMed  CAS  Google Scholar 

  30. Jutooru, I., Chadalapaka, G., Lei, P., & Safe, S. (2010). Inhibition of NFKB and pancreatic cancer cell and tumor growth by curcumin is independent on specificity protein down-regulation. Journal of Biological Chemistry, 285, 25332–25344.

    Article  PubMed  CAS  Google Scholar 

  31. Sluzarc, A., Shenouda, N. S., Sakla, M. S., Drenkhaln, S. K., Narula, A. S., MacDonald, R. S., et al. (2010). Common botanical compounds inhibit the Hedgehog signalling pathway in prostate cancer. Cancer Research, 70, 3382–3390.

    Article  Google Scholar 

  32. Dupont-Gillain, Ch. C., Pamula, E., Denis, F. A., De Cupere, V. M., Dufrene, Y. F., & Rouxhet, P. G. (2004). Controlling the supramolecular organisation of adsorbed collagen layers. Journal of Material Science Materials in Medicine, 15, 347–353.

    Article  CAS  Google Scholar 

  33. Johnson, K. L. (1994). Contact mechanics. Cambridge: Cambridge University Press.

    Google Scholar 

  34. Gupta, K. K., Bharne, S. S., Rathinasamy, K., Naik, N. R., & Panda, D. (2006). Dietary antioxidant curcumin inhibits microtubule assembly through tubulin binding. FEBS Journal, 273, 5320–5332.

    Article  PubMed  CAS  Google Scholar 

  35. Holy, J. M. (2002). Curcumin disrupts mitotic spindle structure and induces micronucleation in MCF-7 breast cancer cells. Mutation Research, 2002(518), 71–84.

    Article  Google Scholar 

  36. Bannerjee, M., Singh, P., & Panda, D. (2010). Curcumin suppresses the dynamic instability of microtubules, activates the mitotic checkpoint and induces apoptosis in MCF-7 cells. FEBS Journal, 277, 3437–3448.

    Article  Google Scholar 

  37. Larroque, C., Lacroix, B., Galeotti, N., & Jouin, P. (2005). Quantitative and qualitative analysis of tubulin isoforms by mass spectrometry. Molecular and Cell Proteomics., 4, s324.

    Google Scholar 

  38. Bec, N., Lacroix, B., Jouin, P., & Larroque, C. (2006). Study of the native microtubule proteome by MALDI-TOF MS. Molecular and Cell Proteomics., 2006(5), s303.

    Google Scholar 

  39. Saab, M. B., Estephan, E., Bec, N., Larroque, M., Aulombard, R., Cloitre, T., et al. (2011). Multi-microscopic study of curcumin effect on fixed non-malignant and cancerous mammalian epithelial cells. Journal of Biophotonics, 4, 533–543.

    Article  PubMed  CAS  Google Scholar 

  40. Kunwar, A., Barik, A., Mishra, B., Rathinasamy, K., Pandey, R., & Priyadarsini, K. I. (2008). Quantitative cellular uptake, localization and cytotoxicity of curcumin in normal and tumor cells. Biochimica et Biophysica Acta, 1780, 673–679.

    Article  PubMed  CAS  Google Scholar 

  41. Schaaf, C., Shan, B., Buchfelder, M., Losa, M., Kreutzer, J., Rachinger, W., et al. (2009). Curcumin acts as anti-tumorigenic and hormone-suppressive agent in murine and human pituitary tumour cells in vitro and in vivo. Endocrine-Related Cancer, 16, 1339–1350.

    Article  PubMed  CAS  Google Scholar 

  42. Prasanth, R., Nair, G., & Girish, C. M. (2011). Enhanced endocytosis of nano-curcumin in nasopharyngeal cancer cells: An atomic force microscopy study. Applied Physics Letters, 99, 163706. doi:10.1063/1.3653388.

    Article  Google Scholar 

  43. Li, Q. S., Lee, G. Y., Ong, C. N., & Lim, C. T. (2008). AFM indentation study of breast cancer cells. Biochemical and Biophysical Research Communications, 2008(374), 609–613.

    Article  Google Scholar 

  44. Beil, M., Micoulet, A., von Wichert, G., Paschke, S., Walther, P., Omary, M. B., et al. (2003). Sphingosylphosphorylcholine regulates keratin network architecture and visco-elastic properties of human cancer cells. Nature Cell Biology, 2003, 803–811.

    Article  Google Scholar 

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Authors and Affiliations

  1. Laboratoire Charles Coulomb UMR 5221, Université Montpellier 2, 34095, Montpellier, France

    Marie-belle Saab, Marta Martin, Elias Estephan & Csilla Gergely

  2. CNRS, Laboratoire Charles Coulomb UMR 5221, 34095, Montpellier, France

    Marie-belle Saab, Marta Martin, Elias Estephan & Csilla Gergely

  3. EA 4203, UFR Odontologie, Université Montpellier 1, 34193, Montpellier Cedex 5, France

    Elias Estephan & Frédéric Cuisinier

  4. IRCM/INSERM896, Centre Régional de Lutte contre le Cancer Val d’Aurelle - Paul Lamarque, Université Montpellier 1, 34298, Montpellier, France

    Nicole Bec & Christian Larroque

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  1. Marie-belle Saab
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Correspondence to Csilla Gergely.

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Saab, Mb., Bec, N., Martin, M. et al. Differential Effect of Curcumin on the Nanomechanics of Normal and Cancerous Mammalian Epithelial Cells. Cell Biochem Biophys 65, 399–411 (2013). https://doi.org/10.1007/s12013-012-9443-1

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