Inhibition by arsenic trioxide of human hepatoma cell growth

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

doi:10.1016/S0304-3835(01)00800-X

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 journal › Article › peer-review

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 language	English (US)
Pages (from-to)	147-153
Number of pages	7
Journal	Cancer Letters
Volume	183
Issue number	2
DOIs	https://doi.org/10.1016/S0304-3835(01)00800-X
State	Published - Sep 26 2002
Externally published	Yes

Keywords

Apoptosis
Arsenic trioxide
Buthionine sulfoximine
Glutathione
Hepatoma

ASJC Scopus subject areas

Oncology
Cancer Research

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10.1016/S0304-3835(01)00800-X

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title = "Inhibition by arsenic trioxide of human hepatoma cell growth",

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.",

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T1 - Inhibition by arsenic trioxide of human hepatoma cell growth

AU - Oketani, Makoto

AU - Kohara, Kazunori

AU - Tuvdendorj, Demidmaa

AU - Ishitsuka, Kenji

AU - Komorizono, Yasuji

AU - Ishibashi, Kazuaki

AU - Arima, Terukatsu

PY - 2002/9/26

Y1 - 2002/9/26

N2 - 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.

AB - 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.

KW - Apoptosis

KW - Arsenic trioxide

KW - Buthionine sulfoximine

KW - Glutathione

KW - Hepatoma

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Inhibition by arsenic trioxide of human hepatoma cell growth

Abstract

Keywords

ASJC Scopus subject areas

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