Inhibition by arsenic trioxide of human hepatoma cell growth

Makoto Oketani, Kazunori Kohara, Demidmaa Tuvdendorj, Kenji Ishitsuka, Yasuji Komorizono, Kazuaki Ishibashi, Terukatsu Arima

Research output: Contribution to journalArticle

67 Scopus citations

Abstract

Arsenic trioxide (As2O3) has been shown to be effective for treatment of patients with refractory or relapsed acute promyelocytic leukemia and a variety of other malignant hematopoetic disorders. We studied the effect of this agent on proliferation of human hepatoma-derived cell lines (SK-Hep-1, HepG2, and HuH7). In HuH7 cells, As2O3 reduced proliferation time- and dose-dependently at 1 and 2 μM, while in SK-Hep-1 and HepG2 cells, As2O3 inhibited proliferation at 2 and 4 μM respectively. Cell cycle analysis by flow cytometry showed that As2O3 induced apoptosis in these hepatoma-derived cells as confirmed by appearance of sub-G1 cells. Sensitivity of hepatoma-derived cells to As2O3 was inversely related to their intracellular glutathione (GSH) and intensity of GSH synthesis. Arsenic sensitivity was restored to relatively resistant cell lines when GSH was depleted by L-buthionine sulfoximine (BSO). These results indicate that As2O3 may have therapeutic potential for treatment of hepatocellular carcinoma.

Original languageEnglish (US)
Pages (from-to)147-153
Number of pages7
JournalCancer Letters
Volume183
Issue number2
DOIs
StatePublished - Sep 26 2002

Keywords

  • Apoptosis
  • Arsenic trioxide
  • Buthionine sulfoximine
  • Glutathione
  • Hepatoma

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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  • Cite this

    Oketani, M., Kohara, K., Tuvdendorj, D., Ishitsuka, K., Komorizono, Y., Ishibashi, K., & Arima, T. (2002). Inhibition by arsenic trioxide of human hepatoma cell growth. Cancer Letters, 183(2), 147-153. https://doi.org/10.1016/S0304-3835(01)00800-X