Prevention of microtubule polymerization is considered as one of the promising approaches towards inhibition of cell proliferation, especially in treatment of malignancies. ARSENIC TRIOXIDE, As2O3, is being successfully used in the treatment of human lymphoma, while the mechanism of its therapeutic function is still under investigation. Experiments were designed to determine if indeed As2O3 interferes with polymerization of nanotube microtubule. Microtubules were extracted from sheep brain and their interaction with ARSENIC TRIOXIDE was examined by spectrometery. Electrical conductometry of 2 mM MgSO4 solution containing various concentrations of As2O3 was studied in order to determine their possible interaction. Transmission electron microscopy was used to show microtubule structure in the presence of ARSENIC TRIOXIDE. Fluorometric characteristics of tubulin dimer were examined in presence of varying concentrations of ARSENIC TRIOXIDE. It is concluded that ARSENIC TRIOXIDE interacts with Mg2+ ion around GTPase site of b-tubulin, resulting enhancement of depolymerization of the microtubule polymer.

Background: Although standard first line treatment of acute promyelocytic leukemia is All trans retinoic acid (ATRA) and chemotherapy, some patients relapse and need a second line of treatment. Relapsed cases of promyelocytic leukemia can be salvaged with ARSENIC TRIOXIDE.Methods: Between May 1999 and Jan.2010, we treated 31 relapsed cases of promyelocytic leukemia with ARSENIC TRIOXIDE. These cases relapsed after previous treatment with ATRA and chemotherapy. We applied ARSENIC TRIOXIDE as 0.15 mg/kg iv infusion until complete remission. After achieving complete remission patients received 2-4 consolidation therapy in the same schedule as remission induction.Results: The median age of patients was 27 years. Complete remission rate was 77.4%. We observed four mortalities during remission induction. With a median follow up of 32 months, ten more relapses occurred. Two year disease-free survival and overall survival for the entire cohort was 54.6% and 81.1%, respectively.Conclusion: Our result is the same as other studies. Thus, we suggest that ARSENIC TRIOXIDE can be used as salvage therapy in patients who relapsed.Despite a good complete remission rate, the relapse rate during the first two years of treatment is high and hematopoietic stem cell transplantation should be considered after achieving complete remission.

Background: Multiple myeloma is a plasma cell dyscrasia characterized by proliferation of plasma cells in bone marrow associated with the production of monoclonal immunoglobulin’s or M-protein. Nowadays, current treatments for this disease include bone marrow transplantation and the use of alkylating agents, other chemotherapy drugs such as antracyclines and also corticosteroids. In recent years, the use of an old medication, ARSENIC TRIOXIDE, formerly approved for treatment of acute promyelocytic leukemia has been considered for myeloma treatment. Initial studies have shown an apoptotic and growth inhibitory effect of ARSENIC TRIOXIDE on myeloma cells. This study was designed and carried out to evaluate the efficacy and possible side effects of ATO on patients with refractory multiple myeloma.Methods and materials: This study carried out on myeloma patients whose diseases were at least refractory to two standard treatment regimens. ARSENIC TRIOXIDE was administered as an intravenous infusion at a dose of 0.25 mg/kg/d for 5 d/week during the first 2 consecutive weeks of each 4-week cycle with 2 week rest. Patients who completed one 4-weak cycle were evaluated for response to treatment.Results: 12 patients with median age of 63 years and with refractory disease to conventional treatment regimens, received ARSENIC TRIOXIDE.10 patients tolerated at least one treatment cycle. Evaluation of response to treatment was possible only in 4 patients in whom the disease was stable. 2 patients died during second cycle of treatment. At the end of third cycle one patient had more than 50 percent decrease in serum protein electrophoresis. Only one patient could complete 6 cycles of treatment. During treatment, some adverse events such as increase in liver enzymes, progressive increase in serum creatinine and neutropenia; also, mild side effects including pruritus, nausea and vomiting, lower extremities edema and noninfectious diarrhea were observed.Conclusion: The use of ARSENIC TRIOXIDE is promising in treatment of refractory multiple myeloma and the likelihood of response will be more great if increased number of chemotherapy are used. Albeit, more researches with larger sample size will give more success. Therapy was well tolerated and serious adverse events were observed to a lesser degree.

The effectiveness of ARSENIC TRIOXIDE (ATO) in treating blood diseases is one of the most striking developments in modern medicine. One of the most important benefits of ATO is the failure of bone marrow suppression. ATO has been proposed as a novel and effective medicine for cancer prevention and treatment with various functions including, induction of apoptosis through re-activating the Wnt inhibitor, growth inhibition via activation of phosphatidylinositol 3-kinase (PI3K)/AKT pathway, autophagy stimulation, induction of cell differentiation and angiogenesis via vascular endothelial growth factor A (VEGFA)-VEGFR2-PI3K/ extracellular signal‐ regulated kinase (ERK) signaling path in cancer cells and ATO may be involved in the acetylation of histones and interfering with gene transcription. ATO can increase the synergistic effect in treatment and increased antitumor effects on prostate cancer cells via inhibiting Akt/mTOR signaling pathways, and so, ATO in combination with inhibiting glutathione synthesis can treat bladder cancer epithelial cells effectively.