Marked increase of CYP24A1 mRNA level in hepatocellular carcinoma cell lines following vitamin D administration

Evelin Horvath, Péter Lakatos, Bernadett Balla, János Pál Kósa, Bálint Tóbiás, Hasan Jozilan, Katalin Borka, Henrik Csaba Horváth, Ilona Kovalszky, Ferenc Szalay

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Aim: 1,25-Dihydroxyvitamin D3 (1,25(OH)2D 3) inhibits cell growth and induces apoptosis in numerous types of tumors. We aimed to examine the mRNA and protein expression of 1,25(OH) 2D3-inactivating CYP24A1 and mRNA expression of the activating CYP27B1 enzymes, as well as that of vitamin D receptor (VDR), in hepatocellular carcinoma (HCC) cell cultures in response to 1,25(OH) 2D3 administration. Materials and Methods: Increasing amounts of 1,25(OH)2D3 (0.256-10 nM) were added to cultures of HepG2, Huh-Neo, Hep3B, Huh5-15 human HCC cell lines and cells then incubated for various time periods (30 min-28 h). The mRNA expression was analyzed by real time reverse transcription-polymerase chain reaction (RT-PCR). CYP24A1 protein in HepG2 cells was detected by immuncytochemistry. Results: CYP24A1 mRNA expression significantly (p<0.0001) increased in response to 1,25(OH)2D3 administration in two cell lines: in HepG2 cells, the CYP24A1 mRNA level exhibited 5,300-fold elevation, reaching a maximum value at 8 h; in Huh-Neo cells, the increase was 152-fold that of the baseline value, with the maximum being reached at 14 h. There was no significant change in Hep3B and Huh5-15 cell lines, nor was there any change in CYP27B1 and VDR gene expression in any cell cultures. Immuncytochemistry in HepG2 cells proved that gene activation was followed by CYP24A1 protein synthesis. Conclusion: Our novel data indicate that administration of 1,25(OH)2D3 results in a marked increase of CYP24A1 mRNA expression in some, but not all, human HCC lines in vitro. These differences could be dependent upon the origin of the tumor cells.

Original languageEnglish
Pages (from-to)4791-4796
Number of pages6
JournalAnticancer research
Volume32
Issue number11
Publication statusPublished - Nov 1 2012

Keywords

  • 1,25-dihydroxyvitamin D
  • CYP24A1
  • HepG2
  • Hepatocellular carcinoma
  • mRNA expression

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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