Skip to main content
PMC home page
British Journal of Cancer logoLink to British Journal of Cancer
. 1987 Jan;55(1):41–46. doi: 10.1038/bjc.1987.9

The anti-proliferative effect of lithium chloride on melanoma cells and its reversion by myo-inositol.

J Nordenberg, C Panet, L Wasserman, Z Malik, A Fuchs, K H Stenzel, A Novogrodsky
PMCID: PMC2001569  PMID: 3028460

Abstract

The effect of LiCl on melanoma cell growth and differentiation was studied in mouse and human melanoma cell lines. LiCl markedly inhibited B16 and HT-144 melanoma cell growth in vitro. Clonogenicity in soft agar of the melanoma cells was also markedly inhibited by LiCl. Pretreatment of B16 mouse melanoma cells with LiCl delayed the appearance of melanoma tumours in syngeneic mice. Growth inhibition of cells was accompanied by morphological and biochemical alterations. LiCl induced cell enlargement and formation of dendrite-like structures. The activity of NADPH cytochrome c reductase, an enzymatic marker of endoplasmic reticulum was significantly (2-3 fold) increased. Addition of myo-inositol to cell cultures partially reversed the anti-proliferative and morphological effects of LiCl on melanoma cells. This finding may suggest that the anti-proliferative effect of LiCl is related to its effect on phosphatidylinositol metabolism.

Full text

PDF
41

Images in this article

43Figure 4
on p.43
45Figure 5
on p.45

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Allison J. H., Blisner M. E., Holland W. H., Hipps P. P., Sherman W. R. Increased brain myo-inositol 1-phosphate in lithium-treated rats. Biochem Biophys Res Commun. 1976 Jul 26;71(2):664–670. doi: 10.1016/0006-291x(76)90839-1. [DOI] [PubMed] [Google Scholar]
  2. Allison J. H., Stewart M. A. Reduced brain inositol in lithium-treated rats. Nat New Biol. 1971 Oct 27;233(43):267–268. doi: 10.1038/newbio233267a0. [DOI] [PubMed] [Google Scholar]
  3. BURTON K. A study of the conditions and mechanism of the diphenylamine reaction for the colorimetric estimation of deoxyribonucleic acid. Biochem J. 1956 Feb;62(2):315–323. doi: 10.1042/bj0620315. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Beitner H., Wennersten G. The immediate action of long-wave ultraviolet radiation (UVA) on suprabasal melanocytes in human skin: a transmission electron microscopical study. Acta Derm Venereol. 1983;63(4):328–334. [PubMed] [Google Scholar]
  5. Berridge M. J., Irvine R. F. Inositol trisphosphate, a novel second messenger in cellular signal transduction. Nature. 1984 Nov 22;312(5992):315–321. doi: 10.1038/312315a0. [DOI] [PubMed] [Google Scholar]
  6. Bray J., Turner A. R., Dusel F. Lithium and the mitogenic response of human lymphocytes. Clin Immunol Immunopathol. 1981 May;19(2):284–288. doi: 10.1016/0090-1229(81)90070-2. [DOI] [PubMed] [Google Scholar]
  7. Dousa T., Hechter O. Lithium and brain adenyl cyclase. Lancet. 1970 Apr 18;1(7651):834–835. doi: 10.1016/s0140-6736(70)92429-3. [DOI] [PubMed] [Google Scholar]
  8. Eliason J. F., Fekete A., Odartchenko N. Improving techniques for clonogenic assays. Recent Results Cancer Res. 1984;94:267–275. doi: 10.1007/978-3-642-82295-7_29. [DOI] [PubMed] [Google Scholar]
  9. Friend C., Scher W., Holland J. G., Sato T. Hemoglobin synthesis in murine virus-induced leukemic cells in vitro: stimulation of erythroid differentiation by dimethyl sulfoxide. Proc Natl Acad Sci U S A. 1971 Feb;68(2):378–382. doi: 10.1073/pnas.68.2.378. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Gallicchio V. S., Chen M. G. Influence of lithium on proliferation of hematopoietic stem cells. Exp Hematol. 1981 Aug;9(7):804–810. [PubMed] [Google Scholar]
  11. Hallcher L. M., Sherman W. R. The effects of lithium ion and other agents on the activity of myo-inositol-1-phosphatase from bovine brain. J Biol Chem. 1980 Nov 25;255(22):10896–10901. [PubMed] [Google Scholar]
  12. Hamburger A. W., Salmon S. E. Primary bioassay of human tumor stem cells. Science. 1977 Jul 29;197(4302):461–463. doi: 10.1126/science.560061. [DOI] [PubMed] [Google Scholar]
  13. Hart D. A. Differential potentiation of in vitro lipopolysaccharide stimulation of B-lymphoid cells by lithium and ammonium ions. Cell Immunol. 1982 Jul 15;71(1):159–168. doi: 10.1016/0008-8749(82)90505-6. [DOI] [PubMed] [Google Scholar]
  14. Hart D. A. Evidence that lithium ions can modulate lectin stimulation of lymphoid cells by multiple mechanisms. Cell Immunol. 1981 Mar 1;58(2):372–384. doi: 10.1016/0008-8749(81)90231-8. [DOI] [PubMed] [Google Scholar]
  15. Hori C., Oka T. Induction by lithium ion of multiplication of mouse mammary epithelium in culture. Proc Natl Acad Sci U S A. 1979 Jun;76(6):2823–2827. doi: 10.1073/pnas.76.6.2823. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Huberman E., Heckman C., Langenbach R. Stimulation of differentiated functions in human melanoma cells by tumor-promoting agents and dimethyl sulfoxide. Cancer Res. 1979 Jul;39(7 Pt 1):2618–2624. [PubMed] [Google Scholar]
  17. Leder A., Leder P. Butyric acid, a potent inducer of erythroid differentiation in cultured erythroleukemic cells. Cell. 1975 Jul;5(3):319–322. doi: 10.1016/0092-8674(75)90107-5. [DOI] [PubMed] [Google Scholar]
  18. Levitt L. J., Quesenberry P. J. The effect of lithium on murine hematopoiesis in a liquid culture system. N Engl J Med. 1980 Mar 27;302(13):713–719. doi: 10.1056/NEJM198003273021303. [DOI] [PubMed] [Google Scholar]
  19. Macher B. A., Lockney M., Moskal J. R., Fung Y. K., Sweeley C. C. Studies on the mechanism of butyrate-induced morphological changes in KB cells. Exp Cell Res. 1978 Nov;117(1):95–102. doi: 10.1016/0014-4827(78)90431-7. [DOI] [PubMed] [Google Scholar]
  20. Morley D. C., Jr, Galbraith P. R. Effect of lithium on granulopoiesis in culture. Can Med Assoc J. 1978 Feb 4;118(3):288–290. [PMC free article] [PubMed] [Google Scholar]
  21. Naccarato W. F., Ray R. E., Wells W. W. Biosynthesis of myo-inositol in rat mammary gland. Isolation and properties of the enzymes. Arch Biochem Biophys. 1974 Sep;164(1):194–201. doi: 10.1016/0003-9861(74)90022-8. [DOI] [PubMed] [Google Scholar]
  22. Nordenberg J., Aloni D., Wasserman L., Beery E., Stenzel K. H., Novogrodsky A. Dimethylthiourea inhibition of melanoma cell growth in vitro and in vivo. J Natl Cancer Inst. 1985 Nov;75(5):891–895. doi: 10.1093/jnci/75.5.891. [DOI] [PubMed] [Google Scholar]
  23. Nordenberg J., Kaplansky M., Beery E., Klein S., Beitner R. Effects of lithium on the activities of phosphofructokinase and phosphoglucomutase and on glucose-1,6-diphosphate levels in rat muscles, brain and liver. Biochem Pharmacol. 1982 Mar 15;31(6):1025–1031. doi: 10.1016/0006-2952(82)90338-0. [DOI] [PubMed] [Google Scholar]
  24. PHILLIPS A. H., LANGDON R. G. Hepatic triphosphopyridine nucleotide-cytochrome c reductase: isolation, characterization, and kinetic studies. J Biol Chem. 1962 Aug;237:2652–2660. [PubMed] [Google Scholar]
  25. Ptashne K., Stockdale F. E., Conlon S. Initiation of DNA synthesis in mammary epithelium and mammary tumors by lithium ions. J Cell Physiol. 1980 Apr;103(1):41–46. doi: 10.1002/jcp.1041030107. [DOI] [PubMed] [Google Scholar]
  26. Reese D. H., Gratzner H. G., Block N. L., Politano V. A. Control of growth, morphology, and alkaline phosphatase activity by butyrate and related short-chain fatty acids in the retinoid-responsive 9-1C rat prostatic adenocarcinoma cell. Cancer Res. 1985 May;45(5):2308–2313. [PubMed] [Google Scholar]
  27. Rybak S. M., Stockdale F. E. Growth effects of lithium chloride in BALB/c 3T3 fibroblasts and Madin-Darby canine kidney epithelial cells. Exp Cell Res. 1981 Dec;136(2):263–270. doi: 10.1016/0014-4827(81)90004-5. [DOI] [PubMed] [Google Scholar]
  28. Scher W., Preisler H. D., Friend C. Hemoglobin synthesis in murine virus-induced leukemic cells in vitro. 3. Effects of 5-bromo-2'-deoxyuridine, dimethylformamide and dimethylsulfoxide. J Cell Physiol. 1973 Feb;81(1):63–70. doi: 10.1002/jcp.1040810108. [DOI] [PubMed] [Google Scholar]
  29. Simmons J. L., Fishman P. H., Freese E., Brady R. O. Morphological alterations and ganglioside sialyltransferase activity induced by small fatty acids in HeLa cells. J Cell Biol. 1975 Aug;66(2):414–424. doi: 10.1083/jcb.66.2.414. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Wang Y. C., Pandey G. N., Mendels J., Frazer A. Effect of lithium on prostaglandin F1-stimulated adenylate cyclase activity of human platelets. Biochem Pharmacol. 1974 Feb 15;23(4):845–855. doi: 10.1016/0006-2952(74)90215-9. [DOI] [PubMed] [Google Scholar]
  31. Wasserman L., Kessler-Icekson G. A simple method for the preparation of permanent slides from cell cultures. Stain Technol. 1984 Nov;59(6):353–354. doi: 10.3109/10520298409113880. [DOI] [PubMed] [Google Scholar]

Articles from British Journal of Cancer are provided here courtesy of Cancer Research UK

RESOURCES