title: Inhibition by arsenic trioxide of human hepatoma cell growth.
abstract: Arsenic trioxide (As(2)O(3)) 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, As(2)O(3) reduced proliferation time- and dose-dependently at 1 and 2 microM, while in SK-Hep-1 and HepG2 cells, As(2)O(3) inhibited proliferation at 2 and 4 microM respectively. Cell cycle analysis by flow cytometry showed that As(2)O(3) induced apoptosis in these hepatoma-derived cells as confirmed by appearance of sub-G(1) cells. Sensitivity of hepatoma-derived cells to As(2)O(3) 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 As(2)O(3) may have therapeutic potential for treatment of hepatocellular carcinoma.
authors.affiliation: The Second Department of Internal Medicine, Faculty of Medicine, Kagoshima University, Kagoshima, Japan. oketani@m2.kufm.kagoshima-u.ac.jp
authors.forename: Makoto
authors.initials: M
authors.lastname: Oketani
authors.forename: Kazunori
authors.initials: K
authors.lastname: Kohara
authors.forename: Demidmaa
authors.initials: D
authors.lastname: Tuvdendorj
authors.forename: Kenji
authors.initials: K
authors.lastname: Ishitsuka
authors.forename: Yasuji
authors.initials: Y
authors.lastname: Komorizono
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Ishibashi
authors.forename: Terukatsu
authors.initials: T
authors.lastname: Arima
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000494:pharmacology*; D006528:Carcinoma, Hepatocellular / Q000517:prevention & control*; D002453:Cell Cycle; D002455:Cell Division / Q000187:drug effects; D004396:Coloring Agents / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D010087:Oxides / Q000494:pharmacology*; D013778:Tetrazolium Salts / Q000494:pharmacology; D013844:Thiazoles / Q000494:pharmacology; D013997:Time Factors; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D001152:Arsenicals; D004396:Coloring Agents; D010087:Oxides; D013778:Tetrazolium Salts; D013844:Thiazoles; C022616:thiazolyl blue; D005978:Glutathione; D000077237:Arsenic Trioxide