Skip to main content
Log in

Induction of differentiation in the cultured F9 teratocarcinoma stem cells by triterpene acids

  • Original Papers
  • Experimental Oncology
  • Published:
Journal of Cancer Research and Clinical Oncology Aims and scope Submit manuscript

Abstract

The effects of the triterpene acids, ursolic acid and oleanolic acid, on the differentiation of F9 teratocarcinoma stem cells were studied. These agents caused the morphological change of F9 cells into endoderm cells, as did retinoic acid (RA). Moreover, expression of laminin B1, type IV collagen and retinoic acid receptor β (RARβ) increased in ursolic-and oleanolic-acid treated F9 cells. Since these agents are structurally similar to the glucocorticoid hormone, we studied the effects of dexamethasone, a synthetic glucocorticoid, on F9 cells. Dexamethasone also induced the morphological change and altered the expression of laminin B1, type IV collagen, and RARβ in F9 cells. In addition, transcription of glucocorticoid receptor was detected after treatment with these three agents. According to Southwestern blot analysis, a 94-kDa protein, thought to be a glucocorticoid receptor, was detected in F9 cells treated with these agents. In a gelshift assay, we identified protein factors binding to the glucocorticoid-responsive element (GRE) in the nuclear proteins from F9 cells treated with ursolic or oleanolic acid. The binding activity of the GRE-binding protein disappeared on the addition of unlabeled GRE oligonucleotide. Taken together, these results suggest that UA and OA can induce the differentiation of F9 cells and may regulate the expression of differentiation-specific genes, probably by forming a complex with the glucocorticoid receptor or its analogous nuclear receptor.

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

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

Abbreviations

UA:

Ursolic acid

OA:

oleanolic acid

RARβ:

retinoic acid receptor β

GRE:

glucoeorticoid-responsive element

References

  • Bradford MM (1976) A rapid and sensitive method for quantification of microgram quantities of protein utilizing the principles of proteindye binding. Anal Biochem 72:248–254

    Google Scholar 

  • Breitman TR, He R (1990) Combinations of retinoic acid with either sodium butyrate, dimethyl sulfoxide, or hexamethylene bisacetamide synergistically induce differentiation of the human myeloid leukemia cell line HL60. Cancer Res 50:6268–6273

    Google Scholar 

  • Chandler VL, Maler BA, Yamamoto KR (1983) DNA sequences bound specifically by glucocorticoid receptor in vitro render a heterologous promoter hormone responsive in vivo. Cell 33:489–499

    Google Scholar 

  • Chomczynski P, Sacchi N (1987) Single-step method of RNA isolation by acid-guanidinium thiocyanate-phenol-choloform extraction. Anal Biochem 162:156–159

    Google Scholar 

  • Dignam JD, Lebowitz RM, Roeder RG (1983) Accurate transcription initiation by RNA polymerase II in a soluble extract from isolated mammalian nuclei. Nucleic Acids Res 11:1475–1489

    Google Scholar 

  • Evans RM (1988) The steroid and thyroid hormone receptor superfamily. Science 240:889–895

    Google Scholar 

  • Feinberg AP, Vogelstein B (1984) Technique for radiolabeling DNA restriction endonuclease fragments to high specific activity. Anal Biochem 137:255–267

    Google Scholar 

  • Grover A, Adamson ED (1986) Evidence for the expression of an early common biochemical pathway in the differentiation of F9 cells into visceral and parietal endoderm: modulation by cyclic AMP. Dev Biol 114:492–503

    Google Scholar 

  • Hong CI, Kirisits AJ, Buchheit DJ, Nechaev A, West CR (1986) 1-β-d-Arabinofuranosylcytosine conjugates of thioether phospholipids as a new class of potential antitumor drugs. Cancer Drug Deliv 3:101–113

    Google Scholar 

  • Hong WK, Lippman SM, Itri LM, Karp DD, Lee JS, Byers RM, Schantz SP, Kramer AM, Lotan R, Peter LJ, Dimery IW, Brown BW, Goepfert H (1990) Prevention of second primary tumors with isotretinoin in squamous-cell carcinoma of the head and neck. N Engl J Med 323:795–801

    Google Scholar 

  • Lee JS, Newman RA, Lippman SM, Huber MH, Minor T, Raber MN, Krakoff IH, Hong WK (1993) Phase I evaluation of all-trans-retinoic acid in adults with solid tumors. J Clin Oncol 11:959–966

    Google Scholar 

  • Madan AP, Defranco DB (1983) Bidirectional transport of glucocorticoid receptors across the nuclear envelope. Proc Natl Acad Sci USA 90:3588–3592

    Google Scholar 

  • Marotti KR, Brown GD, Strickland S (1985) Two-stage hormonal control of type IV collagen mRNA levels during differentiation of F9 teratocarcinoma cells. Dev Biol 108:26–31

    Google Scholar 

  • Nishino H, Nishino A, Takayasu J, Hasegawa T, Iwashima A, Hirabayashi K, Iwata S, Shibaa S (1988) Inhibition of the tumor-promoting action of 12-O-tetradecanoylphorbol-13-acetate by some oleananetype triterpenoid compounds. Cancer Res 48:5210–5215

    Google Scholar 

  • Ohigashi H, Takamura H, Koshimizu H, Tokuda H, Ito Y (1986) Search for possible antitumor promoters by inhibition of 12-O-tetradecanoylphorbol-13-acetate-induced Epstein-Barr virus activation; ursolic acid and oleanolic acid from an anti-inflammatory Chinese medicinal plant,Glechoma hederaceae L. Cancer Lett 30:143–151

    Google Scholar 

  • Sambrook J, Fritsch EF, Maniatis T (1989) Condition for hybridization of oligonucleotide probes, in: Molecular cloning: a laboratory manual, 2nd edn. Cold Spring Harbor, NY, pp 11.45–11.57

  • Scheidereit C, Geisse S, Westphal HM, Beato M (1983) The glucocorticoid receptor binds to defined nucleotide sequences near the promoter of mouse mammary tumor. Nature 304:749–752

    Google Scholar 

  • Silva CM, Tully DB, Petch LA, Jewell CM, Cidlowski JA (1987) Amplication of a protein-blotting procedure to the study of human glucocorticoid receptor interactions with DNA. Proc Natl Acad Sci USA 84:1744–1748

    Google Scholar 

  • Sporn MB, Roberts AB (1983) Role of retinoids in differentiation and carcinogenesis. Cancer Res 43:3034–3040

    Google Scholar 

  • Stevens VL, Owens NF, Winton EF, Kinkade JM, Merill AH (1990) Modulation of retinoic acid-induced differentiation of human leukemia (HL-60) cells by serum factors and sphinganine. Cancer Res 50:222–226

    Google Scholar 

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

    Google Scholar 

  • Strickland S, Sawey MJ (1980) Studies on the effect of retinoids on the differentiation of teratocarcinoma cells in vitro and in vivo. Dev Biol 78:76–85

    Google Scholar 

  • Strickland S, Smith KK, Marotti KR (1980) Hormonal induction of differentiation in teratocarcinoma stem cells: generation of parietal endoderm by retinoic acid and dibutyryl cyclic AMP. Cell 21:347–355

    Google Scholar 

  • Tanaka T, Moriomoto S, Nonaka G, Nishioka I, Yokozawa T, Chung HY, Oura H (1989) Magnesium and ammonium-potassium lithospermates B, the active principles having a uremia-preventive effect fromSalvia miltiorrhiza. Chem Pharm Bull (Tokyo) 37:340–344

    Google Scholar 

  • Tokuda H, Ohigashi H, Koshimizu K, Ito Y (1986) Inhibitory effects of ursolic acid and oleanolic acid on skin tumor promotion by 12-O-tetradecanoylphorbol-13-acetate. Cancer Lett 33:279–285

    Google Scholar 

  • Umehara K, Takagi R, Kuroyanagi M, Ueno A, Taki T, Chen YJ (1992) Studies on differentiation-inducing activities of triterpenes. Chem Pharm Bull (Tokyo) 40:401–405

    Google Scholar 

  • Verma AK, Slaga TJ, Wertz PW, Mueller GC, Boutwell RK (1980) Inhibition of skin tumor promotion by retinoic acid and its metabolite 5,6-epoxy-retinoic acid. Cancer Res 40:2367–2371

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Lee, HY., Chung, HY., Kim, KH. et al. Induction of differentiation in the cultured F9 teratocarcinoma stem cells by triterpene acids. J Cancer Res Clin Oncol 120, 513–518 (1994). https://doi.org/10.1007/BF01221027

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01221027

Key words

Navigation