Springer Nature is making SARS-CoV-2 and COVID-19 research free. View research | View latest news | Sign up for updates

Retinoids and cancer

  • 66 Accesses

  • 99 Citations

Summary

The early and recent investigations in the field of retinoids and cancer are reviewed. The retinoids, including natural vitamin A compounds and their synthetic analogs, present a new class of substances exerting a prophylactic and a therapeutic effect both in certain experimental tumor models and in certain clinical conditions of preneoplastic and neoplastic lesions. Because of a particular physiological mechanism of action, the retinoids offer a new approach to the cancer problem, which is different from those of surgery, X-ray therapy, conventional chemotherapy, and immunotherapy.

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

References

  1. 1.

    Adamo, S., Akalovsky, I., Luca, L. M. de: Retinoic acid-induced changes in saturation density and adhesion of transformed mouse fibroblasts. Proc. Am. Assoc. Cancer Res. 19, 27 (1978)

  2. 2.

    Bard, D. R., Lasnitzki, I.: Toxicity of anti-carcinogenic retinoids in organ culture. Br. J. Cancer 35, 115–119 (1977)

  3. 3.

    Becci, P. J., Thompson, H. J., Grubbs, C. J., Squire, R. A., Brown, C. C., Sporn, M. B., Moon, R. C.: Inhibitory effect of 13-cis-retinoic acid on urinary bladder carcinogenesis induced in C 57 BL/6 mice by N-butyl-N-(4-hydroxybutyl)-nitrosamine. Cancer Res. 38, 4463–4466 (1978)

  4. 4.

    Bollag, W.: Vitamin A and vitamin A acid in the prophylaxis and therapy of epithelial tumors. Int. J. Vitam. Nutr. Res. 40, 299–314 (1970)

  5. 5.

    Bollag, W.: Therapy of chemically induced skin tumors of mice with vitamin A palmitate and vitamin A acid. Experientia 27, 90–92 (1971a)

  6. 6.

    Bollag, W.: Effects of vitamin A acid on transplantable and chemically induced tumors. Cancer Chemother. Rep. 55, 53–58 (1971b)

  7. 7.

    Bollag, W.: Vitamin-A-Säure in der Tumortherapie. Tierexperimentelle Untersuchungen über die Wirkung von Vitamin-A-Säure auf Tumoren. Schweiz. Med. Wochenschr. 101, 11–17 (1971c)

  8. 8.

    Bollag, W.: Prophylaxis of chemically induced papillomas and carcinomas of mouse skin by vitamin A acid. Experientia 28, 1219–1220 (1972a)

  9. 9.

    Bollag, W.: Prophylaxis of chemically induced benign and malignant epithelial tumors by vitamin A acid (retinoic acid). Eur. J. Cancer 8, 689–693 (1972b)

  10. 10.

    Bollag, W.: Antitumor effect of a new retinoic acid analog. Experientia 30, 1198–1199 (1974a)

  11. 11.

    Bollag, W.: Therapeutic effects of an aromatic retinoic acid analog on chemically induced skin papillomas and carcinomas of mice. Eur. J. Cancer 10, 731–737 (1974b)

  12. 12.

    Bollag, W.: Prophylaxis of chemically induced epithelial tumors with an aromatic retinoic acid analog (Ro 10-9359). Eur. J. Cancer 11, 721–724 (1975a)

  13. 13.

    Bollag, W.: Therapy of epithelial tumors with an aromatic retinoic acid analog. Chemotherapy 21, 236–247 (1975b)

  14. 14.

    Bollag, W., Ott, F.: Therapy of actinic keratoses and basal cell carcinomas with local application of vitamin A acid. Cancer Chemother. Rep. 55, 59–60 (1971a)

  15. 15.

    Bollag, W., Ott, F.: Vitamin-A-Säure in der Tumortherapie. Lokalbehandlung von Praekanzerosen und Basalzellkarzinomen der Haut mit Vitamin-A-Säure. Schweiz. Med. Wochenschr. 101, 17–18 (1971b)

  16. 16.

    Chopra, D. P., Wilkoff, L. J.: Inhibition and reversal by β-retinoic acid of hyperplasia induced in cultured mouse prostate tissue by 3-methylcholanthrene or N-methyl-N′-nitro-N-nitrosoguanidine. J. Natl. Cancer Inst. 56, 583–589 (1976)

  17. 17.

    Chu, E. W., Malmgren, R. A.: An inhibitory effect of vitamin A on the induction of tumors of forestomach and cervix in the Syrian hamster by carcinogenic polycyclic hydrocarbons. Cancer Res. 25, 884–895 (1965)

  18. 18.

    Chytil, F., Ong, D. E.: Mediation of retinoic acid-induced growth and anti-tumor activity. Nature 260, 49–51 (1976)

  19. 19.

    Cone, M. V., Nettesheim, P.: Effects of vitamin A on 3-methylcholanthrene-induced squamous metaplasias and early tumors in the respiratory tract of rats. J. Natl. Cancer Inst. 50, 1599–1606 (1976)

  20. 20.

    Davies, R. E.: Effect of vitamin A on 7,12-dimethylbenz(a)anthracene-induced papillomas in Rhino mouse skin. Cancer Res. 27, 237–241 (1967)

  21. 21.

    Dennert, G., Lotan, R.: Effects of retinoic acid on the immune system: stimulation of T killer cell induction. Eur. J. Immunol. 8, 23–29 (1978)

  22. 22.

    Dennert, G., Crowley, C., Kouba, J., Lotan, R.: Retinoic acid stimulation of the induction of mouse killer T-cells in allogeneic and syngeneic systems. J. Natl. Cancer Inst. 62, 89–94 (1979)

  23. 23.

    Dickens, M. S., Sorof, S.: Prevention of transformation of mammary gland by retinoid in whole organ culture. Proc. Am. Assoc. Cancer Res. 20, 71 (1979)

  24. 24.

    Dingle, J. T., Lucy, J. A.: Vitamin A, carotenoids and cell function. Biol. Rev. 40, 422–461 (1965)

  25. 25.

    Dion, L. D., Blalock, J. E., Gifford, G. E.: Brief communication: Vitamin A-induced density-dependent inhibition of L-cell proliferation. J. Natl. Cancer Inst. 58, 795–801 (1977)

  26. 26.

    Dion, D. L., Blalock, J. E., Gifford, G. E.: Retinoic acid and the restoration of anchorage dependent growth to transformed mammalian cells. Exp. Cell Res. 117, 15–22 (1978)

  27. 27.

    Dresser, D. W.: Adjuvanticity of vitamin A. Nature 217, 527–529 (1968)

  28. 28.

    Evard, J. P., Bollag, W.: Konservative Behandlung der rezidivierenden Harnblasenpapillomatose mit Vitamin-A-Säure. Schweiz. Med. Wochenschr. 102, 1880–1883 (1972)

  29. 29.

    Feldman, M. K., Foster, R. C.: Inhibition of preneoplastic mammary cell growth by vitamin A. Proc. Am. Assoc. Cancer Res. 20, 181 (1979)

  30. 30.

    Felix, E. L., Loyd, B., Cohen, M. H.: Inhibition of the growth and development of a transplantable murine melanoma by vitamin A. Science 189, 886–888 (1975)

  31. 31.

    Floersheim, G. L., Bollag, W.: Accelerated rejection of skin homografts by vitamin A acid. Transplantation 15, 564–567 (1972)

  32. 32.

    Frigg, M., Torhorst, J.: Autoradiographic and histopathologic studies on the mode of action of an aromatic retinoid (Ro 10-9359) on chemically induced epithelial tumors in Swiss mice. J. Natl. Cancer Inst. 58, 1365–1371 (1977)

  33. 33.

    Fujimaki, Y.: Formation of carcinoma in albino rats fed on deficient diets. J. Cancer Res. 10, 469–477 (1926)

  34. 34.

    Grubbs, C. J., Moon, R. C., Sporn, M. B., Newton, D. L.: Inhibition of mammary cancer by retinyl methyl ether. Cancer Res. 37, 599–602 (1977)

  35. 35.

    Harisiadis, L., Miller, R. C., Hall, E. J., Borek, C.: A vitamin A analogue inhibits radiation-induced oncogenic transformation. Nature 274, 486–487 (1978)

  36. 36.

    Huber, P. R., Geyer, E., Küng, W., Matter, A., Torhorst, J., Eppenberger, U.: Retinoic acid binding protein in human breast cancer and dysplasia. J. Natl. Cancer Inst. 61, 1375–1378 (1978)

  37. 37.

    Jetten, A. M., Jetten, M. E. R.: Possible role of retinoic acid-binding protein in retinoid stimulation of embryonal carcinoma cell differentiation. Nature 278, 180–182 (1979)

  38. 38.

    Jurin, M., Tannock, I. F.: Influence of vitamin A on immunological response. Immunology 23, 283–287 (1972)

  39. 39.

    Kistler, A.: Inhibition of vitamin A action in rat bone cultures by inhibitors of RNA and protein synthesis. Experientia 34, 1159–1161 (1978)

  40. 40.

    Kistler, G. S., Peter, H. J.: Wirkung von zwei Retinoiden auf menschliche Bronchuskarzinome in vivo (nu/nu-Maus) und in vitro. Schweiz. Med. Wochenschr. 109, 847–850 (1979)

  41. 41.

    Koch, H.: Biochemical treatment of precancerous oral lesions: The effectiveness of various analogues of retinoic acid. J. Maxillofac. Surg. 6, 59–63 (1978)

  42. 42.

    Koch, H., Schettler, D.: Klinische Erfahrungen mit Vitamin-A-Säure-Derivaten bei der Behandlung von Leukoplakien der Mundschleimhaut. Dtsch. Zahnaerztl. Z. 28, 623–627 (1973)

  43. 43.

    Lasnitzki, I.: Growth pattern of the mouse prostate gland in organ culture and its response to sex hormones, vitamin A and 3-methylcholanthrene. Natl. Cancer Inst. Monogr. 12, 381–403 (1963)

  44. 44.

    Lasnitzki, I.: Reversal of methylcholanthrene-induced changes in mouse prostates in vitro by retinoic acid and its analogues. Br. J. Cancer 34, 239–248 (1976)

  45. 45.

    Lasnitzki, I., Goodman, D. S.: Inhibition of the effects of methylcholanthrene on mouse prostate in organ culture by vitamin A and its analogs. Cancer Res. 34, 1564–1571 (1974)

  46. 46.

    Levij, I. S., Polliack, A.: Potentiating effect of vitamin A on 9,10-dimethyl-1,2-benzanthracene carcinogenesis in the hamster cheek pouch. Cancer 22, 300–306 (1968)

  47. 47.

    Levinson, S. S., Wolf, G.: The effect of vitamin A acid on glycoprotein synthesis in skin tumors (keratoacanthomas). Cancer Res. 32, 2248–2252 (1972)

  48. 48.

    Lotan, R.: Inhibition of the in vitro proliferation and DNA synthesis in murine S 91 melanoma cells by retinoic acid and its synthetic analogs. Proc. Am. Assoc. Cancer Res. 19, 4 (1978)

  49. 49.

    Lotan, R.: Different susceptibilities of human melanoma and breast carcinoma cell lines to retinoic acid-induced growth inhibition. Proc. Am. Assoc. Cancer Res. 20, 14 (1979)

  50. 50.

    Lotan, R., Dennert, G.: Stimulatory effects of vitamin A analogs on induction of cell-mediated cytotoxicity in vivo. Cancer Res. 39, 55–58 (1979)

  51. 51.

    Lotan, R., Nicolson, G. L.: Inhibitory effects of retinoic acid or retinyl acetate on the growth of untransformed, transformed and tumor cells in vitro. J. Natl. Cancer Inst. 59, 1717–1722 (1977)

  52. 52.

    Lotan, R., Giotta, G., Nork, E., Nicolson, G. L.: Characterization of the inhibitory effects of retinoids on the in vitro growth of two malignant murine melanomas. J. Natl. Cancer Inst. 60, 1035–1041 (1978)

  53. 53.

    Luca, L. M. de: The direct involvement of vitamin A in glycosyl transfer reactions of mammalian membranes. Vitam. Horm. 35, 1–57 (1977)

  54. 54.

    Luca, L. M. de, Adamo, S., Bhat, P. V., Sasak, W., Silverman-Jones, C. S., Akalovsky, I., Frot-Coutaz, J. P., Fletcher, T. R., Chader, G. J.: Recent developments in studies on biological functions of vitamin A in normal and transformed tissues. Pure Appl. Chem. 51, 581–591 (1979a)

  55. 55.

    Luca, L. M. de, Sasak, W., Adamo, S., Akalovsky, I., Bhat, P. V.: Structure-function relationship of retinoids in retinoid-induced adhesion of cultured spontaneously-transformed mouse fibroblasts (BALB/C 3 T 12-3 cells). Proc. Am. Assoc. Cancer Res. 20, 151 (1979b)

  56. 56.

    McMichael, H.: Inhibition of growth of Shope rabbit papilloma by hypervitaminosis A. Cancer Res. 25, 947–955 (1965)

  57. 57.

    Mahrle, G., Berger, H.: Protective effect of aromatic retinoic acid analog on skin tumor. J. Invest. Dermatol. 70, 235 (1978)

  58. 58.

    Matter, A., Bollag, W.: A fine-structural study on the therapeutic effect of an aromatic retinoid on chemically induced skin papillomas of the mouse. Eur. J. Cancer 13, 831–838 (1977)

  59. 59.

    Mayer, H., Bollag, W., Hänni, R., Rüegg, R.: Retinoids, a new class of compounds with prophylactic and therapeutic activities in oncology and dermatology. Experientia 34, 1105–1119 (1978)

  60. 60.

    Merriman, R. L., Bertman, J. S.: Reversible inhibition by retinoids of 3-methylcholanthrene-induced neoplastic transformation in C3H/10 T 1/2 clone 8 cells. Cancer Res. 39, 1661–1666 (1979)

  61. 61.

    Micksche, M., Cerni, C., Kokron, O., Titscher, R., Wrba, H.: Stimulation of immune response in lung cancer patients by vitamin A therapy. Oncology 34, 234–238 (1977)

  62. 62.

    Moon, R. C., Grubbs, C. J., Sporn, M. B.: Inhibition of 7,12-dimethyl-benz(a)anthracene-induced mammary carcinogenesis by retinyl acetate. Cancer Res. 36, 2626–2630 (1976)

  63. 63.

    Moon, R. C., Grubbs, C. J., Sporn, M. B., Goodman, D. G.: Retinyl acetate inhibits mammary carcinogenesis induced by N-methyl-N-nitrosourea. Nature 267, 620–621 (1977)

  64. 64.

    Moon, R. C., Thompson, H. J., Becci, P. J., Grubbs, C. J., Gander, R. J., Newton, D. L., Smith, J. M., Phillips, S. L., Henderson, W. R., Mullen, L. T., Brown, C. C., Sporn, M. B.: N-(4-Hydroxyphenyl) retinamide, a new retinoid for prevention of breast cancer in the rat. Cancer Res. 39, 1339–1346 (1979)

  65. 65.

    Moore, T.: Vitamin A, pp. 301–313. Amsterdam: Elsevier 1957

  66. 66.

    Mori, S.: The changes in the para-ocular glands which follow the administration of diets low in fat-soluble A; with notes on the effect of the same diets on the salivary glands and the mucosa of the larynx and trachea. Bull. Johns Hopkins Hosp. 33, 357–359 (1922)

  67. 67.

    Newberne, P. M., Suphakarn, V.: Preventive role of vitamin A in colon carcinogenesis in rats. Cancer 40, 2553–2556 (1977)

  68. 68.

    Newton, D. L., Frolik, C. A., Roberts, A. B., Smith, J. M., Sporn, M. B., Nürrenbach, A., Paust, J.: Biological activity and metabolism of the retinoid axerophthene. Cancer Res. 38, 1734–1738 (1978)

  69. 69.

    Niles, R. M., Logue, M. P.: Retinoid acid increases cyclic AMP-dependent protein kinase activity in B 16-F1 mouse melanoma cells. Proc. Am. Assoc. Cancer Res. 20, 166 (1979)

  70. 70.

    Ong, D. E., Chytil, F.: Presence of cellular retinol and retinoic acid-binding proteins in experimental tumors. Cancer Lett. 2, 25–30 (1976)

  71. 71.

    Ong, D. E., Page, D. L., Chytil, F.: Retinoic acid-binding protein: Occurrence in human tumors. Science 190, 60–61 (1975)

  72. 72.

    Ong, D. D., Markert, C., Chiu, J. F.: Cellular binding proteins for vitamin A in colorectal adenocarcinoma of rat. Cancer Res. 38, 4422–4426 (1978)

  73. 73.

    Patt, L. M., Itaya, K., Hakomori, S. I.: Retinol induces density-dependent growth inhibition and changes in glycolipids and LETS. Nature 273, 379–381 (1978)

  74. 74.

    Peck, G. L., Olsen, T. G., Butkus, D., Pandya, M., Arnaud-Battandier, J., Yoder, F., Levis, W. R.: Treatment of basal cell carcinomas with 13-cis-retinoic acid. Proc. Am. Assoc. Cancer Res. 20, 56 (1979)

  75. 75.

    Port, C. D., Sporn, M. B., Kaufman, D. G.: Prevention of lung cancer in hamsters by 13-cis-retinoic acid. Proc. Am. Assoc. Cancer Res. 16, 21 (1975)

  76. 76.

    Prutkin, L.: The effect of vitamin A acid on tumorigenesis and protein production. Cancer Res. 28, 1021–1030 (1968)

  77. 77.

    Rettura, G., Schittek, A., Hardy, M., Levenson, S. M., Demetrion, A., Seifter, E.: Brief communication: Antitumor action of vitamin A in mice inoculated with adenocarcinoma cells. J. Natl. Cancer Inst. 54, 1489–1491 (1975)

  78. 78.

    Rowe, N. A., Gorlin, R. J.: The effect of vitamin A deficiency upon experimental oral carcinogenesis. J. Dent. Res. 38, 72–83 (1959)

  79. 79.

    Ryssel, H. J., Brunner, K. W., Bollag, W.: Die perorale Anwendung von Vitamin-A-Säure bei Leukoplakien, Hyperkeratosen und Plattenepithelkarzinomen: Ergebnisse und Verträglichkeit. Schweiz. Med. Wochenschr. 101, 1027–1030 (1971)

  80. 80.

    Saffiotti, U., Montesano, R., Sellakumar, A. R., Borg, S. A.: Experimental cancer of the lung. Inhibition by vitamin A of the induction of tracheobronchial squamous metaplasia and squamous cell tumors. Cancer 20, 857–864 (1967)

  81. 81.

    Sani, B. P., Corbett, T. H.: Retinoic acid-binding protein in normal tissues and experimental tumors. Cancer Res. 37, 209–213 (1977)

  82. 82.

    Sani, B. P., Titus, B. C.: Retinoic acid-binding protein in experimental tumors and in tissues with metastatic tumor foci. Cancer Res. 37, 4031–4034 (1977)

  83. 83.

    Sani, B. P., Titus, B. C., Banerjee, C. K.: Determination of binding affinities of retinoids to retinoic acid-binding protein and serum albumin. Biochem. J. 171, 711–717 (1978)

  84. 84.

    Seifter, E., Zisblatt, M., Levine, N., Rettura, G.: Inhibitory action of vitamin A on a murine sarcoma. Life Sci. 13, 945–952 (1973)

  85. 85.

    Sporn, M. B., Clamon, G. H., Dunlop, N. M., Newton, D. L., Smith, J. M., Saffiotti, U.: Activity of vitamin A analogues in cell cultures of mouse epidermis and organ cultures of hamster trachea. Nature 253, 47–50 (1975)

  86. 86.

    Sporn, M. B., Dunlop, N. M., Newton, D. L., Henderson, W. R.: Relationship between structure and activity of retinoids. Nature 263, 110–113 (1976)

  87. 87.

    Sporn, M. B., Squire, R. A., Brown, C. C., Smith, J. M., Wenk, M. L., Springer, S.: 13-cis-retinoic acid: Inhibition of bladder carcinogenesis in the rat. Science 195, 487–489 (1977)

  88. 88.

    Squire, R. A., Sporn, M. B., Brown, C. C., Smith, J. M., Wenk, M. L., Springer, S.: Histopathological evaluation of the inhibition of rat bladder carcinogenesis by 13-cis-retinoic acid. Cancer Res. 37, 2930–2936 (1977)

  89. 89.

    Strickland, S., Mahdavi, V.: The induction of differentiation in teratocarcinoma stem cells by retinoic acid. Cell 15, 393–403 (1978)

  90. 90.

    Todaro, G. J., DeLarco, J. E., Sporn, M. B.: Retinoids block phenotypic cell transformation produced by sarcoma growth factor. Nature 276, 272–274 (1978)

  91. 91.

    Trown, P. W., Buck, M. J., Hansen, R.: Inhibition of growth and regression of a transplantable rat chondrosarcoma by three retinoids. Cancer Treat. Rep. 60, 1647–1653 (1976)

  92. 92.

    Verma, A. K., Boutwell, R. K.: Vitamin A acid (retinoic acid), a potent inhibitor of 12-0-tetradecanoyl-phorbol-13-acetate-induced ornithine decarboxylase activity in mouse epidermis. Cancer Res. 37, 2196–2201 (1977)

  93. 93.

    Verma, A. K., Rice, H. M., Shapas, B. G., Boutwell, R. K.: Inhibition of 12-0-tetradecanoyl-phorbol-13-acetate-induced ornithine decarboxylase activity in mouse epidermis by vitamin A analogs (retinoids). Cancer Res. 38, 793–801 (1978)

  94. 94.

    Verma, A. K., Shapas, B. G., Rice, H. M., Boutwell, R. K.: Correlation of the inhibition by retinoids of tumor promoter-induced mouse epidermal ornithine decarboxylase activity and of skin tumor promotion. Cancer Res. 39, 419–425 (1979)

  95. 95.

    Wolbach, S. B., Howe, P. R.: Tissue changes following deprivation of fat-soluble A-vitamin. J. Exp. Med. 42, 753–778 (1925)

  96. 96.

    Wolbach, S. B., Howe, P. R.: Vitamin A deficiency in the guinea-pig. Arch. Pathol. 5, 239–253 (1928)

  97. 97.

    Yamamoto, N., Bister, K., Zur Hausen, H.: Retinoic acid inhibition of Epstein-Barr virus induction. Nature 278, 553–554 (1979)

Download references

Author information

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Bollag, W. Retinoids and cancer. Cancer Chemother. Pharmacol. 3, 207–215 (1979). https://doi.org/10.1007/BF00254733

Download citation

Keywords

  • Cancer Research
  • Therapeutic Effect
  • Clinical Condition
  • Retinoid
  • Tumor Model