Arsenic trioxide induces apoptosis in cisplatin-sensitive and -resistant ovarian cancer cell lines

Abstract

Arsenic trioxide (As(2)O(3)), has been used for centuries in traditional Chinese medicine; it has considerable efficacy in the treatment of relapsed acute promyelocytic leukemia, inducing partial differentiation and promoting apoptosis of malignant promyelocytes. Although a number of studies have demonstrated that As(2)O(3) has potent activity against cell growth in a series of leukemia cell lines, little information is available regarding this compound's effect on cell growth in solid tumor cell lines. In this study, we investigated the effects of As(2)O(3)in vitro on ovarian cancer cell lines sensitive (3AO) and resistant (3AO/CDDP) to cisplatin. The 3-(4,5-dimethy-thiazoyl-2-yl)-2,5-diphenyl-tetrazolium bromide assay was used to evaluate cytotoxicity. Flow cytometric analysis was used to determine the apoptosis, cell cycle distribution. We clearly demonstrated that As(2)O(3) induced cell apoptosis and inhibition of cell growth in both the cell lines. Furthermore, we identified that As(2)O(3)-induced apoptosis involved Fas pathway. As(2)O(3) is an active agent against ovarian cancer cells and could be effective in the clinical treatment of ovarian cancer.

Enhancement of Arsenic Trioxide (As2O3)- Mediated Apoptosis Using Berberine in Human Neuroblastoma SH-SY5Y Cells

“…Berberine was also shown to inhibit DNA and protein synthesis, cell cycle progress of arrest, and the in vitro growth of a number of human cancer cell lines, however, the molecular mechanisms underlying berberine-induced apoptosis are not yet well defined 7) . Although As2O3 has potent activity against cell growth in a series of leukemia cell lines, little information is available regrading this compound's effect on cell growth in solid tumor cell lines 14) . The mechanisms of As2O3 cytotoxicity are not known completely, but preclinical studies have provided insight into the processes involved.…”

“…The mechanisms include cellular differentiation, induction of apoptosis, and inhibition of angiogenesis 4) . As2O3-induced apoptosis has been described in three major apoptotic mechanisms; mitogen-activated protein (MAP) kinase, activation of caspase pathway, and production of ROS [2][3][4]14,24) . Because As2O3 at higher concentrations induces many side effects (ventricular arrhythmia, skin reaction, peripheral neuropathy, electrolyte changes, leukocytosis, hepatic dysfunction, GI reactions, etc.)…”

“…ROS are free radicals that react with all biological macromolecules, modify the structure and function of proteins as well as cause oxidative damage to DNA 12,14) . Hydrogen peroxide (H2O2) is a common intermediate in the oxidative metabolic precess, which has been shown to induce DNA damage in human cells 4,5,27,28) .…”

Redox status of thioredoxin-1 (TRX1) determines the sensitivity of human liver carcinoma cells (HepG2) to arsenic trioxide-induced cell death

“…Arsenic trioxide (As 2 O 3 ) has been used clinically to effectively treat acute promyelocytic leukemia (APL) [1,2] and other types of cancers [3,4]. This success prompts studies to investigate the molecular mechanisms of action underlying the clinic effectiveness.…”

Synergistic interaction between tetra-arsenic oxide and paclitaxel in human cancer cells in vitro

“…Previous studies have shown that ATO induces apoptosis not only in human leukemic cells but also in human solid tumor cells (8)(9)(10)(11)(12). Activation of capase-3 following downregulation of bcl-2 and degradation of PML-RAR· protein was shown in the leukemic cancer cell lines (13,14).…”