Skip to main content

The chemoprevention of cancer by dietary carotenoids: Studies in mouse and human cells

  • Conference paper
Oxidative Stress and Aging

Part of the book series: Molecular and Cell Biology Updates ((MCBU))

  • 175 Accesses

Summary

In many epidemiologic studies a decreased risk of cancer has been associated with the consumption of diets rich in fruits and in green and yellow vegetables. Of the many components of such a diet the content of carotenoids, particularly β-carotene, has been most consistently linked to decreased risk. The biological mechanism for such protection is at present unclear; multiple possibilities exist: carotenoids are potent antioxidants and oxidative stress is known to contribute to carcinogenesis; many carotenoids can be converted to retinoids, known cancer preventive agents at several anatomic sites; finally carotenoids may possess additional actions in mammalian cells. Experimental studies have been inhibited by difficulties in delivering these molecules to target cells. A novel delivery system, using THE as solvent, has been developed and the activity of several carotenoids tested in mouse 10T1/2 cells. Carotenoids have been shown to: (a) inhibit plasma membrane lipid-oxidation; (b) inhibit carcinogen-induced neoplastic transformation; (c) cause up-regulated expression at the message and protein level of connexin43, a gene coding for the structural unit of a gap junction. This latter activity was statistically correlated with the ability to inhibit neoplastic transformation. While protection from carcinogen-induced neoplastic transformation cannot be directly studied in human cells, Cx43 expression is also up-regulated in human fibroblasts, suggesting that carotenoids have chemopreventive action in humans. We have proposed that increased junctional communication is mechanistically linked to inhibition of transformation. In this model, the gap junction serves as a conduit for growth regulatory signals from normal to carcinogen-initiated cells, thereby suppressing their transformation.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Agarwal, C. and Eckert, R.L. (1990) Immortalization of human keratinocytes by simian virus 40 large T-antigen alters keratin gene response to retinoids. Cancer Res. 50: 5947–5953.

    PubMed  CAS  Google Scholar 

  • Ames, B.N., Shigenaga, M.K. and Gold, L.S. (1993) DNA lesions, inducible DNA repair, and cell division: Three key factors in mutagenesis and carcinogenesis. Environmental Health Perspectives 101 Suppl. 5: 35–44.

    Google Scholar 

  • Bertram, J.S., Kolonel, L.N. and Meyskens, F.L. (1987) Rationale and stratagies for chemoprevention of cancer in humans. Cancer Res. 47: 3012–3031.

    PubMed  CAS  Google Scholar 

  • Bertram, J.S., Hossain, M.Z., Pung, A. and Rundhaug, J.E. (1989) Development of in vitro systems for chemoprevention research. Prey. Med. 18: 562–575.

    Article  CAS  Google Scholar 

  • Bertram, J.S. (1990) Role of gap junctional cell/cell communication in the control of proliferation and neoplastic transformation. Radiat. Res. 123: 252–256.

    Article  PubMed  CAS  Google Scholar 

  • Bertram, J.S., Pung, A., Churley, M., Kappock, T.J.I., Wilkins, L.R. and Cooney, R.V. (1991) Diverse carotenoids protect against chemically induced neoplastic transformation. Carcinogenesis 12: 671–678.

    Article  PubMed  CAS  Google Scholar 

  • Beyer, E.C., Paul, D.L. and Goodenough, D.A. (1987) Connexin 43: A protein from rat heart homologous to a gap junction protein from liver. J. Cell Biol. 105: 2621–2629.

    Article  PubMed  CAS  Google Scholar 

  • Beyer, E.C., Paul, D.L. and Goodenough, D.A. (1990) Connexin family of gap junction proteins. J. Membrane Biol. 116: 187–194.

    Article  CAS  Google Scholar 

  • Blumberg, P.M., Pettit, G.R., Warren, B.S., Szallasi, A., Schuman, L.D., Sharkey, N.A., Nakakuma, H., Dell’Aquila, M.L. and De Vries, D.J. (1989) The protein kinase C pathway in tumor promotion. Prog. Clin. Biol. Res. 298: 201–212.

    PubMed  CAS  Google Scholar 

  • Devasagayam, T.P.A., Werner, T., Ippendorf, H., Martin, H.-D. and Sies, H. (1992) Synthetic carotenoids, novel polyene polyketones and new capsorubin isomers as efficient quenchers of singlet molecular oxygen. Photochemistry and Photobiology 55: 511–514.

    Article  PubMed  CAS  Google Scholar 

  • Eghbali, B., Kessler, J.A., Reid, L.M., Roy, C. and Spray, D.C. (1991) Involvement of gap junctions in tumorigenesis: transfection of tumor cells with connexin 32 cDNA retards growth in vivo. Proc. Natl. Acad. Sci. USA 88: 10701–10705.

    Article  CAS  Google Scholar 

  • Fletcher, W.H., Byus, C.V. and Walsh, D.A. (1987) Receptor-mediated action without receptor occupancy: a function for cell-cell communication in ovarian follicles. Adv. Exp. Med. Biol. 219: 299–323.

    PubMed  CAS  Google Scholar 

  • Gerster, H. (1993) Anticarcinogenic effect of common carotenoids. Int. J. Vitam. Nutr. Res. 63: 93–121.

    PubMed  CAS  Google Scholar 

  • Guthrie, S.C. and Gilula, N.B. (1989) Gap junctional communication and development. Trends. Neurosci. 12: 1216.

    Google Scholar 

  • Greenberg, E.R., Baron, J.A., Stukel, T.A., Stevens, M.M., Mandel, J.S., Spencer, S.K., Elias, P.M., Lowe, N., Nierenberg, D.W., Bayrd, G., Vance, J.C., Freeman, D.H., Clendenning, W.E. and Kwan, T. (1990) A clinical trial of 13-carotene to prevent basal-cell and squamous-cell cancers of the skin. N. Engl. J. Med. 323: 789–795.

    Article  PubMed  CAS  Google Scholar 

  • Heinonen, O.P., Albanes, D. et al. (1994) The effect of vitamin E and 13-carotene on the incidence of lung cancer and other cancers in male smokers. N. Engl. J. Med. 330: 1029–1035.

    Google Scholar 

  • Hoffmann, B., Lehmann, J.M., Zhang, X., Hermann, T., Husmann, M., Graupner, G. and Pfahl, M. (1990) A retinoic acid receptor-specific element controls the retinoic acid receptor-(3 promoter. Mol. Endocrinol. 4: 1727–1736.

    Article  PubMed  CAS  Google Scholar 

  • Hong, W.K. and Itri, L.M. (1994) Retinoids and human cancer. In: M.B. Sporn, A.B. Roberts and D.S. Goodman (eds):The Retinoids, Raven Press, New York, pp 597–630.

    Google Scholar 

  • Hossain, M.Z, Wilkens, L.R., Mehta, P.P., Loewenstein, W. and Bertram, J.S. (1989) Enhancement of gap junctional communication by retinoids correlates with their ability to inhibit neoplastic transformation. Carcinogenesis 10: 1743–1748.

    Article  PubMed  CAS  Google Scholar 

  • Loewenstein, W.R. (1987) The cell-to-cell channel of gap junctions. Cell 48: 725–726.

    Article  PubMed  CAS  Google Scholar 

  • Mangelsdorf, D.J., Umesono, K. and Evans, R.M. (1994) The Retinoid Receptors. In: M.B. Sporn, A.B. Roberts and D.S. Goodman (eds):The Retinoids, Raven Press, New York pp 319–350.

    Google Scholar 

  • Mehta, P.P., Bertram, J.S. and Loewenstein, W.R. (1986) Growth inhibition of transformed cells correlates with their junctional communication with normal cells. Cell 44: 187–196.

    Article  PubMed  CAS  Google Scholar 

  • Mehta, P.P., Bertram, J.S. and Loewenstein, W.R. (1989) The actions of retinoids on cellular growth correlate with their actions on gap junctional communication. J. Cell Biol. 108: 1053–1065.

    Article  PubMed  CAS  Google Scholar 

  • Merriman, R. and Bertram, J.S. (1979) Reversible inhibition by retinoids of 3-methylcholanthrene-induced neoplastic transformation in C3H/10T 1/2 cells. Cancer Res. 39: 1661–1666.

    PubMed  CAS  Google Scholar 

  • Moon, R.C. (1989) Comparative aspects of carotenoids and retinoids as chemopreventive agents for cancer. J. Nutr. 119: 127–134.

    PubMed  CAS  Google Scholar 

  • Moon, R.C., Mehta, R.G. and Rao, K.V.N. (1994) Retinoids and cancer in experimental animals. In: M.B. Sporn, A.B. Roberts and D.S. Goodman (eds):The Retinoids, Raven Press, New York, pp 573–596.

    Google Scholar 

  • Peto, R., Doll, R., Buckley, J.D. and Sporn, M.B. (1981) Can dietary 13-carotene materially reduce human cancer rates? Nature 290: 201–208.

    Article  PubMed  CAS  Google Scholar 

  • Poor, C.L., Bierer, T.L., Merchen, N.R., Fahey, G.C., Jr., Murphy, M.R. and Erdman, J.W., Jr. (1992) Evaluation of the preruminant calf as a model for the study of human carotenoid metabolism. J. Nutr. 122: 262–268.

    PubMed  CAS  Google Scholar 

  • Pung, A., Rundhaug, J.E., Yoshizawa, C.N. and Bertram, J.S. (1988) 13-carotene and canthaxanthin inhibit chemically-and physically-induced neoplastic transformation in 10T1/2 cells. Carcinogenesis 9: 1533–1539.

    Google Scholar 

  • Pung, A., Franke, A., Zhang, L.X., Ippendorf, H., Martin, H.D., Sies, H. and Bertram, J.S. (1993) A synthetic carotenoid inhibits carcinogen-induced neoplastic transformation and enhances gap junctional communication. Carcinogenesis 14: 1001–1005.

    Article  PubMed  CAS  Google Scholar 

  • Reznikoff, C.A., Bertram, J.S., Brankow, D.W. and Heidelberger, C. (1973) Quantitative and qualitative studies of chemical transformation of cloned C3H mouse embryo cells sensitive to postconfluence inhibition of cell division. Cancer Res. 33: 2339–2349.

    Google Scholar 

  • Rogers, M., Berestecky, J.M., Hossain, M.Z., Guo, H.M., Kadle, R., Nicholson, B.J. and Bertram, J.S. (1990) Retinoid-enhanced gap junctional communication is achieved by increased levels of connexin 43 mRNA and protein. Mol. Carcinog. 3: 335–343.

    Article  PubMed  CAS  Google Scholar 

  • Sâez, J.C., Connor, J.A., Spray, D.C. and Bennett, M.V.L. (1989) Hepatocyte gap junctions are permeable to the second messenger inositol 1,4,5-trisphosphate, and to calcium ions. Proc. Natl. Acad. Sci. USA 86: 2708–2712.

    Article  PubMed  Google Scholar 

  • Yagi, K. (1987) Lipid peroxides and human diseases. Chem. Phys. Lipids 457: 337–351.

    Article  Google Scholar 

  • Zhang, L., Cooney, R.V. and Bertram, J.S. (1992) Carotenoids up-regulate connexin 43 gene expression independent of their pro-vitamin A or antioxidant properties. Cancer Res. 52: 5707–5712.

    PubMed  CAS  Google Scholar 

  • Zhang, L.-X., Cooney, R.V. and Bertram, J.S. (1991) Carotenoids enhance gap junctional communication and inhibit lipid peroxidation in C3H/10T1/2 cells: Relationship to their cancer chemopreventive action. Carcinogenesis 12: 2109–2114.

    Article  PubMed  CAS  Google Scholar 

  • Zhu, D., Caveney, S., Kidder, G.M. and Naus, C.C.G. (1991) Transfection of C6 glioma cells with connexin 43 cDNA: analysis of expression, intercellular coupling, and cell proliferation. Proc. Natl. Acad. Sci. USA 88: 1883–1887.

    Article  PubMed  CAS  Google Scholar 

  • Zhu, D., Kidder, G.M., Caveney, S. and Naus, C.C.G. (1992) Growth retardation in glioma cells cocultured with cells overexpressing a gap junction protein. Proc. Natl. Acad Sci. USA 89: 10218–10221.

    Article  PubMed  CAS  Google Scholar 

  • Ziegler, R.G. (1991) Vegetables, fruits and carotenoids and the risk of cancer. Am. J. Clin. Nutr. 53: 251S - 2595.

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 1995 Birkhäuser Verlag Basel/Switzerland

About this paper

Cite this paper

Bertram, J.S. (1995). The chemoprevention of cancer by dietary carotenoids: Studies in mouse and human cells. In: Cutler, R.G., Packer, L., Bertram, J., Mori, A. (eds) Oxidative Stress and Aging. Molecular and Cell Biology Updates. Birkhäuser Basel. https://doi.org/10.1007/978-3-0348-7337-6_22

Download citation

  • DOI: https://doi.org/10.1007/978-3-0348-7337-6_22

  • Publisher Name: Birkhäuser Basel

  • Print ISBN: 978-3-0348-7339-0

  • Online ISBN: 978-3-0348-7337-6

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics