Elsevier

Differentiation

Volume 68, Issues 2–3, October 2001, Pages 133-140
Differentiation

ORIGINAL ARTICLE
Curcumin-induced differentiation of mouse embryonal carcinoma PCC4 cells

https://doi.org/10.1046/j.1432-0436.2001.680207.xGet rights and content

Abstract

Curcumin, a natural component of turmeric extracted from the rhizomes of Curcuma longa, is known to exhibit a number of biological properties. In the present study, curcumin, at low concentration, was shown to induce differentiation in embryonal carcinoma cell line PCC4. In response to curcumin, PCC4 cells ceased to proliferate and showed cell cycle arrest at G1 phase after 4 hours of treatment, followed by their differentiation which is characterized by increase of nuclear/cytoplasmic ratio. The expression of hsp 70 was also seen upon 8 h of curcumin treatment, and it remained constant up to 48 h. Differentiated cells also expressed a series of differentiation markers such as lamin A, well-established actin, and keratin cytoskeleton. We used mRNA differential display analysis to identify the genes that are regulated during curcumin-induced differentiation of PCC4 cells. We cloned and sequenced three partial cDNAs that were differentially expressed in normal and differentiated cells. Sequence comparison of one downregulated cDNA (A1) has shown homology to a gene present on mouse chromosome five, while the two upregulated cDNA (C1 and C7) are homologous to several mouse ESTs clones from organs of mesodermal origin. We have identified the full-length coding sequence of the C1 fragment with a putative amino acid sequence. Tissue-specific Northern with RNA from adult mouse organs with the C1 fragment alone showed hybridization with mRNA from several tissues, whereas the same Northern with only the coding sequence showed expression of C1 gene mainly in the adult kidney. Homology search revealed that C1 sequence is part of the 3′ UTR and may be common to several genes expressed in many tissues. Thus, curcumin appears to differentiate embryonal carcinoma cell PCC4, and one of the upregulated genes seems to be expressed mainly in the adult kidney.

References (44)

  • W.K. Lo et al.

    Spatiotemporal distribution of zonulae adherens and associated actin bundles in both epithelium and fiber cells during chicken lens development

    Exp Eye Res

    (2000)
  • E.V. Maytin et al.

    Keratin 10 gene expression during differentiation of mouse epidermis requires transcription factors C/EBP and AP-2

    Dev Biol

    (1999)
  • T. Pierce et al.

    Neuronal differentiation of NT2/D1 teratocarcinoma cells is accompanied by a loss of lamin A/C expression and an increase in lamin B1 expression

    Exp Neurol

    (1999)
  • J. Rossant et al.

    The relationship between embryonic, embryonal carcinoma and embryo-derived stem cells

    Cell Differ

    (1984)
  • S. Singh et al.

    Activation of transcription factor NF-kappa B is suppressed by curcumin (diferuloylmethane) [corrected]

    J Biol Chem

    (1995)
  • J.A. Sokoloski et al.

    Induction of the differentiation of HL-60 promyelocytic leukemia cells by nonsteroidal anti-inflammatory agents in combination with low levels of vitamin D3

    Leuk Res

    (1998)
  • K.S. Bisht et al.

    Differentiation of mouse embryonal carcinoma cells PCC4 by heat shock and the kinetics of induction of heat shock proteins

    Ind J Biochem Mol Biol

    (1994)
  • Y.C. Chen et al.

    Induction of HSP 70 gene expression by modulation of Ca(+2) ion and cellular p53 protein by curcumin in colorectal carcinoma cells

    Mol Carcinog

    (1996)
  • S. Chomczynski et al.

    Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction

    Anal Biochem

    (1986)
  • A.H. Conney et al.

    Some perspectives on dietary inhibition of carcinogenesis: studies with curcumin and tea

    Proc Soc Exp Biol Med

    (1997)
  • S. Gibbs et al.

    Characterization of the human spr2 promoter – induction after UV irradiation or TPA treatment and regulation during differentiation of cultured primary keratinocytes

    Nucleic Acids Res

    (1990)
  • M. Goldberg et al.

    The nuclear lamina: molecular organization and interaction with chromatin

    Crit Rev Eukaryot Gene Expr

    (1999)
  • View full text