The cell cycle related apoptotic susceptibility to arsenic trioxide is associated with the level of reactive oxygen species

Gao, Fei; Yi, Jing; Yuan, Jinliang; Shi, Gui Ying; Tang, Xue

doi:10.1038/sj.cr.7290206

Cited by 54 publications

(40 citation statements)

References 36 publications

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“…It is possible that the hypoxic environment contributes to cellular conditions supporting the cytotoxic effect of As 2 O 3 . For instance, oxidative stress with generation of ROS is believed to be one of the major pathways for arsenic-mediated cytotoxicity (18,42,43), although the mechanism(s) and pathway(s) whereby these ROS are generated remain largely unknown. There is also growing evidence that mitochondrial ROS are produced during hypoxia (44).…”

Section: Discussionmentioning

confidence: 99%

Multidrug-resistant neuroblastoma cells are responsive to arsenic trioxide at both normoxia and hypoxia

Karlsson

Edsjö

Påhlman

et al. 2005

Molecular Cancer Therapeutics

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Despite intensive treatment, the outcome of high-risk neuroblastoma patients is poor with acquired multidrug resistance as an important cause. Previously, our group has shown that arsenic trioxide (As 2 O 3 ) kills multidrugresistant neuroblastoma cells in vitro and in vivo at clinically tolerable doses. Regions of tissue hypoxia often arise in aggressive solid tumors, and hypoxic tumors exhibit augmented invasiveness and metastatic ability in several malignancies. Furthermore, hypoxia may impair the treatment efficiency; therefore, we have studied the cytotoxic effect of As 2 O 3 on neuroblastoma cells grown under normoxic as well as hypoxic (1% oxygen) conditions. At both normoxia and hypoxia, 2 and 4 Mmol/L As 2 O 3 induced evident cell death in the drug-sensitive SH-SY5Y and IMR-32 cells as well as in the multidrugresistant SK-N-BE(2)c (with a mutated p53) and SK-N-FI cells after 72 hours of exposure. In contrast, the conventional chemotherapeutic drug etoposide showed lowered efficiency in hypoxic IMR-32 cells. In accordance with our previously published results, although not to the same extent as in their normoxic counterparts, Bax is proteolytically cleaved also in neuroblastoma cells exposed to As 2 O 3 at hypoxia. This suggests that similar molecular mechanisms are involved in As 2 O 3 -induced neuroblastoma cell death during hypoxia compared with normoxia. Together, our results support As 2 O 3 as a potential candidate drug as a complement to conventional treatments for high-risk neuroblastoma patients and perhaps also for patients with other multidrug-resistant solid tumors. [Mol Cancer Ther 2005;4(7):1128 -35]

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Section: Discussionmentioning

confidence: 99%

Multidrug-resistant neuroblastoma cells are responsive to arsenic trioxide at both normoxia and hypoxia

Karlsson

Edsjö

Påhlman

et al. 2005

Molecular Cancer Therapeutics

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“…Production of ROS was determined using 6-carboxy-2V ,7V -dihydrofluorescein-diacetate (Molecular Probes, Eugene, OR) and FACS analysis as described (19,20). HeLa cells, 1 Â 10 6 , were seeded into 100-mm plates.…”

Section: Methodsmentioning

confidence: 99%

Dihydroartemisinin Is Cytotoxic to Papillomavirus-Expressing Epithelial Cells In vitro and In vivo

et al. 2005

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Nearly all cervical cancers are etiologically attributable to human papillomavirus (HPV) infection and pharmaceutical treatments targeting HPV-infected cells would be of great medical benefit. Because many neoplastic cells (including cervical cancer cells) overexpress the transferrin receptor to increase their iron uptake, we hypothesized that irondependent, antimalarial drugs such as artemisinin might prove useful in treating HPV-infected or transformed cells. We tested three different artemisinin compounds and found that dihydroartemisinin (DHA) and artesunate displayed strong cytotoxic effects on HPV-immortalized and transformed cervical cells in vitro with little effect on normal cervical epithelial cells. DHA-induced cell death involved activation of the mitochondrial caspase pathway with resultant apoptosis. Apoptosis was p53 independent and was not the consequence of drug-induced reductions in viral oncogene expression. Due to its selective cytotoxicity, hydrophobicity, and known ability to penetrate epithelial surfaces, we postulated that DHA might be useful for the topical treatment of mucosal papillomavirus lesions. To test this hypothesis, we applied DHA to the oral mucosa of dogs that had been challenged with the canine oral papillomavirus. Although applied only intermittently, DHA strongly inhibited viral-induced tumor formation. Interestingly, the DHA-treated, tumor-negative dogs developed antibodies against the viral L1 capsid protein, suggesting that DHA had inhibited tumor growth but not early rounds of papillomavirus replication. These findings indicate that DHA and other artemisinin derivatives may be useful for the topical treatment of epithelial papillomavirus lesions, including those that have progressed to the neoplastic state. (Cancer Res 2005; 65(23): 10854-61)

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“…The complete case history of the subjects was recorded and the subjects who had no other illness and were not under any medication were included in this study. They were grouped as euthyroid (16), hypothyroid (17), and hyperthyroid (16) based on the thyroid function tests done by electrochemiluminescence, evaluating the free thyroxine (fT 4 ) and thyroid stimulating hormone (TSH) levels.…”

Section: Methodsmentioning

confidence: 99%

“…ROS production was detected using the dye DCFH-DA (Sigma) essentially according to the procedure described earlier (16)(17)(18). DCFH-DA is a stable non-fluorescent, cell permeable compound, which on penetrating the cell is converted to DCFH by intracellular esterases, is trapped within the cell, and is stable for a few hours.…”

Section: Flow-cytometric Measurement Of Rosmentioning

confidence: 99%

Flow‐cytometric analysis of reactive oxygen species in peripheral blood mononuclear cells of patients with thyroid dysfunction

Sarkar

Varshney

Chopra

et al. 2005

Cytometry Part B Clinical

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Background: Thyroid hormones are major regulators of energy metabolism and increased levels of the hormones (hyperthyroidism) results in an increase in the metabolic rate. Thyroid dysfunction causing alteration in hormone secretion leads to perturbations in the metabolic status. The hypermetabolic state may cause increased generation of reactive oxygen species (ROS), leading to oxidative stress in these patients. This study was carried out to verify our proposition by measuring the ROS in the terminally differentiated cells like the peripheral blood mononuclear cells of the patients.Methods: Flow-cytometric analysis of the ROS was carried out using 2 0 ,7 0 dichlorofluorescein diacetate in the isolated peripheral blood mononuclear cells of the subjects.Results: ROS generation was found to be 3-folds higher in hyperthyroids as compared with euthyroids and hypothyroids and this was not found to be gender specific.Conclusions: Hyperthyroidism results in ROS generation in patients, which can be detected flow cytometrically in the peripheral blood mononuclear cells. Hence, this could complement the other thyroid function tests facilitating the diagnosis and design of appropriate therapy. q 2005 International Society for Analytical Cytology

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The cell cycle related apoptotic susceptibility to arsenic trioxide is associated with the level of reactive oxygen species

Cited by 54 publications

References 36 publications

Multidrug-resistant neuroblastoma cells are responsive to arsenic trioxide at both normoxia and hypoxia

Multidrug-resistant neuroblastoma cells are responsive to arsenic trioxide at both normoxia and hypoxia

Dihydroartemisinin Is Cytotoxic to Papillomavirus-Expressing Epithelial Cells In vitro and In vivo

Flow‐cytometric analysis of reactive oxygen species in peripheral blood mononuclear cells of patients with thyroid dysfunction

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