Summary
Treatment of cultured HeLa cells with 5 mM sodium butyrate causes an inhibition of growth as well as extensive chemical and morphological differentiation. Lysosomal enzyme activity changes have been associated with both normal and neoplastic growth as well as many aspects of the neoplastic process. The comparative ultrastructural results show that the butyrate-treated cells have a more extensive internal membraneous system than the untreated cells, whereas other organelles seem unaffected by the butyrate treatment. Methods for the histochemical localization of lysosomal acid phosphatase show a twofold increase in particulate reaction product in the butyrate-treated HeLa cells. Isolation of lysosomes followed by a comparative enzyme analysis shows a two to three fold increase in acid phosphatase activity per cell after 24 h of butyrate treatment, as well as three to four fold increase in β-glucuronidase activity. These increases reverse within 24 h of removal of the butyrate from the culture medium. These results as interpreted suggest that butyrate treatment may be preventing sublethal autolysis by arresting the leakage of the lysosomal enzymes from the lysosome into the cytosol and thus allowing the cell to chemically and morphologically differentiate.
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Allison, A. C.; Dingle, J. T. Lysosomes and cancer. In: Fell, H. B., eds. Lysosomes in biology and pathology, vol. 196. New York: American Elsevier Publishing Co.; 1969:178–204.
Allison, A. C. Lysosomes in cancer cell. J. Clin. Path. Suppl. (Roy. Cell Path.) 7: 43–50; 1972.
Burger, M. M. Proteolytic enzymes initiating cell division and escape from contact inhibition of growth. Nature 227: 170–171; 1970.
DeDuve, C. Lysosomes, a new group of cytoplasmic particles. In: Hayashi, T., ed. Subcellular particles. New York: Ronald Press; 1959; 128–159.
Ezzel, R. M.; Szego, C. M. Luteinizing hormonal accelerated redistribution of lysosome-like organelles preceding dissolution of nuclear envelope in rat occytes maturing in vitro. J. Cell Biol. 82: 264–277; 1979.
Fishman, P. H.; Bradley, R. H.; Henneberry, R. C. Butyrate induced glycolipid biosynthesis in HeLa cells: properties of the induced sialotransferase. Arch. Biochem. Biophys. 172: 618–626; 1974.
Fiszer-Szafarz, B.; Nadal, C. Lysosomal enzyme activities in the regenerating rat liver. Cancer Res. 37: 354–357; 1977.
Ginsburg, E.; Salomon, D.; Streevalsan, T.; et al. Growth inhibition and morphological changes caused by lipophilic acids in mammalian cells. Proc. Natl Acad. Sci. USA 70: 2157–2161; 1973.
Gomori, G. Histochemical methods for acid phosphatase. J. Histochem. Cytochem. 4: 453–461; 1956.
Hagopian, H. K. Effect of n-butyrate on DNA synthesis in chick fibroblasts and HeLa cells. Cell 12: 855–860; 1977.
Henneberry, R. C.; Fishman, P. H.; Freese, E. Morphological changes in cultured mammalian cells: prevention by the calcium ionophore A23187 Cell 5: 1–9; 1975.
Henneberry, R. C.; Fishman, P. H. Morphological and biochemical differentiation in HeLa cells. Exp. Cell Res. 103: 55–62; 1976.
Horvat, A.; Acs, G. Induction of lysosomal enzymes in contact inhibited 3T3 cells. J. Cell Physiol. 83: 59–68; 1973.
Kaplow, L. S.; Burnstone, M. S. Cytochemical demonstration of acid phosphatase in hematopoietic cells in health and in various hematological disorders using azo dye techniques. J. Histochem. Cytochem. 12: 805–811; 1964.
Kennedy, A. R.; Little, J. B. Protease inhibitors suppress radiation-induced malignant transformation in vitro. Nature 276: 825–826; 1978.
Korok, T.; Drevon, C. Inhibition of chemical transformation in C3H/10T1/2 cells by protease inhibitors. Cancer Res. 39: 2755–2761; 1976.
Kruh, J. Effects of sodium butyrate, a new pharmacological agent, on cells in culture. Mol. Cell. Biochem. 42: 65–82; 1982.
Lanzerotti, R. H.; Gullino, P. M. Activities and quantities of lysosomal enzymes during mammary tumor regression. Cancer Res. 32: 2679–2685; 1972.
Maciera-Coelho, A.; Garcia-Biraly, E.; Adrian, M. Changes in lysosomal associated structures in human fibroblasts kept in resting phase (35974). Proc. Soc. Exp. Biol. Med. 138: 712–718; 1971.
Maggi, V. A study of lysosomal ACH phosphatase during mitosis in HeLa cells. J. R. Microbiol. Soc. 85: 291–295; 1965.
Nicholson, R. I. Influence of altered lysosomal enzyme activities on the regression of DMBA-induced rat mammary tumors. Eur. J. Cancer 13: 1225–1230; 1977.
Poole, A. R. Tumor lysosomal enzymes and invasive growth. In: Dingle, J. T.; Fell, H. B.; eds. Lysosomes in biology and pathology. New York: American Elsevier Publishing Co.; 1979;304–335.
Poste, G. L. Sublethal autolysis. Exp. Cell Res. 67: 11–16; 1972.
Prasad, K. N.; Sinha, P. K. Effect of sodium butyrate on mammalian cells in culture: a review. In Vitro 12: 125–132; 1976.
Quigley, J. P. Proteolytic enzymes of normal and malignant cells. In: Hynes, R. O., ed. Surfaces of normal and malignant cells. Sussex, England: Wiley; 1979: 247–285.
Schersten, T.; Lundholm, K. Lysosomal enzyme activity in muscle tissue from patients with malignant tumors. Cancer 30: 1246–1251; 1972.
Schneider, F. H. Effects of sodium butyrate on mouse neuroblastoma cells in culture. Biochem. Pharmacol. 25: 2309–2317; 1976.
Shamberger, R. J. Lysosomal enzyme changes in growing and regressing mammary tumors. Biochem. J. 111: 375–383; 1969.
Simmons, J. L.; Fishman, P. H.; Freese, E.; et al. Morphological alterations and gangliosides sialotransferase activity induced by small fatty acids in HeLa cells. J. Cell Biol. 66:414–424; 1975.
Tallman, J. F.; Smith, C. C.; Henneberry, R. C. Induction of functional β-adrenergic receptors in HeLa cells. Proc. Natl. Acad. Sci. USA 74: 873–877; 1977.
Weiss, L.; Holyoke, E. D. Some effect of hypervitaminosis on metastasis of spontaneous breast cancer in mice. J. Natl. Cancer Inst. 43: 1045–1053; 1969.
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This work was supported by National Institute of Health Grant HD 14085-03.
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Kelly, R.E. Sodium butyrate induced alterations in lysosomal enzyme activity. In Vitro Cell Dev Biol 21, 373–381 (1985). https://doi.org/10.1007/BF02623468
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DOI: https://doi.org/10.1007/BF02623468