Arsenic trioxide (As2O3) induces clinical remi ion in acute promyelocytic leukemia (APL) with minimal toxicity and apoptosis in APL-derived 4 cells at low (1 to 2 micromol/L) concentration. We examined the basis for 4 cell se itivity to As2O3 to identify experimental conditio that would render other malignant cells re o ive to low concentratio of As2O3. The intracellular glutathione (GSH) content had a decisive effect on As2O3-induced apoptosis. Highly se itive 4 cells had the lowest GSH and the se itivity of other cell lines was inversely proportional to their GSH content. The t(14;18) B-cell lymphoma cell line had low GSH levels and se itivity to As2O3 at levels slightly higher than in APL cells. Experimental upmodulation of GSH content decreased the se itivity to As2O3. Ascorbic acid and buthionine sulfoxide ( O) decreased GSH to a greater extent, and rendered malignant cells more se itive to As2O3. As2O3-induced apoptosis was not enhanced by ascorbic acid in normal cells, suggesting that the combination of ascorbic acid and As2O3 may be selectively toxic to some malignant cells. Ascorbic acid enhanced the antilymphoma effect of As2O3 in vivo without additional toxicity. Thus, As2O3 alone or administered with ascorbic acid may provide a novel therapy for lymphoma
J Biol Regul Homeost Agents 2000 Apr-Ju 14(2):116-9
As2O3 induces apoptosis of the human B lymphoma cell line MBC-1.
Shen L, Chen TX, Wang YP, Lin Z, Zhao HJ, Zu YZ, Wu G, Ying DM.
Department of Oncology, Shanghai I titute for Pediatric Research, China.
OBJECTIVE: To see how arsenic trioxide (As2O3) affects proliferation of the human B lymphoma cell line MBC-1. METHODS: We studied the effect of As2O3 on MBC-1 cells and its mechanism by morphological o ervation, flow cytometry a ay and DNA gel electrophoresis. RESULTS: As2O3 could upregulate p53 gene expre ion at protein level, inducing cell apoptosis and inhibiting the proliferation of MBC-1 cells. Upregulation of p53 expre ion a ears to be important in the apoptosis of MBC-1 cells. CONCLUSIO : As2O3 can inhibit the proliferation of MBC-1 cells by upregulating p53 gene expre ion, thus inducing apoptosis.
Blood 1999 Jan 1;93(1):278-83
Arsenic trioxide and interferon-alpha synergize to induce cell cycle arrest and apoptosis in human T-cell lymphotropic virus type I-tra formed cells.
Bazarbachi A, El-Sa an ME, Nasr R, Quignon F, Awaraji C, Kersual J, Dianoux L, Zermati Y, Haidar JH, Hermine O, de The H.
Departments of Internal Medicine and Biochemsitry, Human Morphology, and Pathology and Laboratory Medicine, American University of Beirut, Beirut, Lebanon. bazarbac@aub.edu.lb
Human T-cell lymphotropic virus type I (HTLV-I) is the causative agent of adult T-cell leukemia/lymphoma (ATL). ATL is an aggre ive proliferation of matur