Small-molecule c-Myc inhibitor, 10058-F4, inhibits proliferation, downregulates human telomerase reverse transcriptase and enhances chemosensitivity in human hepatocellular carcinoma cells

Che Pin Lin, Jean-Dean Liu, Jyh-Ming Chow, Chien Ru Liu, Hsingjin-Eugene Liu

Research output: Contribution to journalArticle

78 Citations (Scopus)

Abstract

c-Myc oncogene is critical for the development of hepatocellular carcinoma. Given the successful use of small-molecule inhibitors on cancers, targeting c-Myc with small-molecule inhibitors represents a promising approach. The potential of using small-molecule c-Myc inhibitor, 10058-F4, was evaluated on hepatocellular carcinoma cell lines, HepG2 and Hep3B cells. HepG2 cells were more sensitive to 10058-F4 than Hep3B cells, as demonstrated by reduced cell viability, marked morphological changes and decreased c-Myc levels. 10058-F4 arrested the cell cycle (at G0/G1 phase) and induced apoptosis upon extended treatment. These observations might be attributable to the increased cyclin-dependent kinase inhibitor, p21, and decreased cyclin D3 levels. Besides, 10058-F4 also significantly decreased the α-fetoprotein levels, an indicator for hepatocellular carcinoma differentiation. We further found that 10058-F4 inhibited the transactivation of human telomerase reverse transcriptase, downregulated human telomerase reverse transcriptase expression and abrogated telomerase activity. In addition, pretreatment with 10058-F4 increased the chemosensitivity of HepG2 cells to low-dose doxorubicin, 5-fluorouracil and cisplatin. Therefore, small-molecule c-Myc inhibitors might represent a novel agent, alone or in combination with conventional chemotherapeutic agents, for anti-hepatocellular carcinoma therapy.

Original languageEnglish
Pages (from-to)161-170
Number of pages10
JournalAnti-Cancer Drugs
Volume18
Issue number2
DOIs
Publication statusPublished - Feb 2007

Keywords

  • 10058-F4
  • Hepatocellular carcinoma
  • Human telomerase reverse transcriptase
  • p21
  • Small-molecule c-Myc inhibitor

ASJC Scopus subject areas

  • Pharmacology
  • Cancer Research
  • Oncology

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