Arsenic is a toxic metalloid known to interact with drug-metabolizing enzymes. In the present study, we investigated the effects of arsenic trioxide (As2O3), recently used as an anticancer drug, on the expression of human cytochrome P450 (P450) 1A1, which bioactivates polycyclic aromatic hydrocarbons into mutagenic metabolites. Clinically relevant concentrations (0.25-5 microM) of As2O3 were de...

Cardiotoxicity is an aggravating side effect of many clinical antineoplastic agents such as arsenic trioxide (As2O3), which is the first-line treatment for acute promyelocytic leukemia (APL). Clinically, drug combination strategies are widely applied for complex disease management. Here, an optimized, cardiac-friendly therapeutic strategy for APL was investigated using a combination of As2O3 an...

Although arsenic trioxide (As2O3) has been successfully employed in treatment of patients with APL (acute promyelocytic leukemia), the sensitivity of solid tumor cells to this treatment was much lower than APL cells. The single agent of As2O3 was inefficient for treatment of hepatocellular carcinoma (HCC) in phase II trial demonstrating that new m...

Although mechanisms of arsenic trioxide (As2O3)-induced cell death have been studied extensively in hematologic cancers, those in solid cancers have yet to be clearly defined. In this study, we showed that the translocation of apoptosis-inducing factor (AIF) from mitochondria to the nucleus is required for As2O3-induced cell death in human cervical cancer cells. We also showed that reactive oxy...

BACKGROUND The incidence of low birth weights is increased in offspring of women who are exposed to high concentrations of arsenic in drinking water compared with other women. We hypothesized that effects of arsenic on birth weight may be related to effects on myogenic differentiation. OBJECTIVE We investigated the effects of arsenic trioxide (As2O3) on the myogenic differentiation of myoblas...

Abstract: Arsenic trioxide (As2O3) has cytotoxic effects on several cancer cell lines. However, the molecular mechanisms of action remain to be elucidated. Hence, the aim of the present study was to evaluate the cytotoxicity and genotoxicity induced by As2O3 in a human Jurkat T-cell line using the MTT [3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] and alkaline single cell gel e...

AIM To Quantitatively analyze the nitric oxide (NO) and Ca2+ in apoptosis of esophageal carcinoma cells induced by arsenic trioxide (As2O3). METHODS The cell line SHEEC1, a malignant esophageal epithelial cell induced by HPV in synergy with TPA in our laboratory, was cultured in a serum-free medium and treated with As2O3. Before and after administration of As2O3, NO production in cultured med...

We studied the effects of varying and steady-state concentrations of arsenic trioxide (As2O3) on apoptosis and differentiation of several cell lines in vitro. We also studied the same effects of fluctuating vs constant concentrations of As2O3 in vivo in patients treated with daily 3-hour fast infusions or daily slow, continuous infusions. Intracellular concentrations of arsenic and apoptosis ra...

Arsenic exhibits a differential toxicity to cancer cells. At a high concentration (>5 microM), As2O3 causes acute necrosis in various cell lines. At a lower concentration (0.5-5 microm), it induces myeloid cell maturation and an arrest in metaphase, leading to apoptosis. As2O3-treated cells have features found with both tubulin-assembling enhancers (Taxol) and inhibitors (colchicine). Prior tre...

Standard cytochemical methods were used to investigate the ameliorative effect of melatonin (0.2 mM) on chromosomal aberrations in human lymphocyte cultures induced by arsenic (As2O3, 1.4 μM) and/or fluoride (NaF, 34 μM). As2O3 and/or NaF generated a significant increase in the incidence of chromosomal aberrations as compared to control levels. Combined treatment with As2O3 and NaF induced more...