Topical treatment for human papillomavirus-associated genital warts in humans with the novel tellurium immunomodulator AS101: assessment of its safety and efficacy

Friedman, Michael; Bayer, I.; Letko, I.; Duvdevani, R.; Zavaro-Levy, O.; Ron, B.; Albeck, Michael; Sredni, Benjamin

doi:10.1111/j.1365-2133.2008.08853.x

Cited by 24 publications

(16 citation statements)

References 20 publications

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“…In fact, immunomodulatory, anti-inflammatory, antioxidant, antidepressant-like, and antitumoral properties [17,18,20,43,44] have been attributed to organotellurium compounds. Regarding the pharmacological properties of PEBT, antioxidant and nootropic activities have been reported in vivo [21,22].…”

Section: Discussionmentioning

confidence: 99%

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Involvement of the serotonergic system in the anxiolytic-like effect of 2-phenylethynyl butyltellurium in mice

Quines

Rocha

Sampaio

et al. 2015

Behavioural Brain Research

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Section: Discussionmentioning

confidence: 99%

“…Organotellurium compounds have been reported as antioxidants in several animal models of oxidative stress [14][15][16]. Moreover, these compounds had immunomodulatory and anti-inflammatory actions [17][18][19]. In addition, the vinyl alkynyl telluride class of compounds demonstrated an antidepressant-like action in mice [20].…”

Section: Introductionmentioning

confidence: 99%

Involvement of the serotonergic system in the anxiolytic-like effect of 2-phenylethynyl butyltellurium in mice

Quines

Rocha

Sampaio

et al. 2015

Behavioural Brain Research

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“…The ammonium trichloro (dioxoethylene-o,o’) tellurate compound is a non-toxic immunomodulator that has demonstrated therapeutic efficacy in preclinical studies of cancer (Sredni et al, 1987, 1996, 2004a), hair loss (Sredni et al, 2004b), human papillomavirus (Friedman et al, 2009), ischemic stroke (Okun et al, 2007) and Parkinson’s disease (Sredni et al, 2007). The mechanism(s) of action of AS101 is not fully established, but it does inhibit the production of IL-1β and IL-10, and can directly inhibit caspases 1, 3 and 8 by interacting with thiol groups (Sredni et al, 2004a; Strassmann et al, 1997; Kalechman et al, 2007; Brodisky et al, 2007, 2010).…”

Section: Introductionmentioning

confidence: 99%

Tellurium Compound AS101 Ameliorates Experimental Autoimmune Encephalomyelitis by VLA-4 Inhibition and Suppression of Monocyte and T Cell Infiltration into the CNS

et al. 2013

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Multiple sclerosis (MS) is an inflammatory autoimmune disease of the central nervous system (CNS) involving demyelinating and neurodegenerative processes. Several of the major pathological CNS alterations and behavioral deficits of MS are recapitulated in the experimental autoimmune encephalitis (EAE) mouse model in which the disease process is induced by administration of myelin peptides. Development of EAE requires infiltration of inflammatory cytokine-generating monocytes and macrophages, and auto-reactive T cells, into the CNS. Very late antigen-4 (VLA-4, α4β1) is an integrin molecule that plays a role in inflammatory responses by facilitating the migration of leukocytes across the blood-brain barrier during inflammatory disease, and antibodies against VLA-4 exhibit therapeutic efficacy in mouse and monkey MS models. Here we report that the tellurium compound AS101 (ammonium trichloro (dioxoethylene-o,o’) tellurate) ameliorates EAE by inhibiting monocyte ant T-cell infiltration into the CNS. CD49d is an alpha subunit of the VLA-4 (α4β1) integrin. During the peak stage of EAE, AS101 treatment effectively ameliorated the disease process by reducing the number of CD49d+ inflammatory monocyte/macrophage cells in the spinal cord. AS101 treatment markedly reduced the pro-inflammatory cytokine levels, while increasing anti-inflammatory cytokine levels. In contrast, AS101 treatment did not affect the peripheral populations of CD11b+ monocytes and macrophages. AS101 treatment reduced the infiltration of CD4+ and CD49+/VLA4 T cells. In addition, treatment of T cells from MS patients with AS101 resulted in apoptosis, while such treatment did not affect T cells from healthy donors. These results suggest that AS101 reduces accumulation of leukocytes in the CNS by inhibiting the activity of the VLA-4 integrin, and provide a rationale for the potential use of Tellurium IV compounds for the treatment of MS.

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“…In the last few decades, evidence has been accumulating that OT molecules are promising pharmacological agents. Several reports have been published showing immuno-modulatory, antioxidant, anticancer and anti-inflammatory properties of OT compounds [3][4][5]. Despite the growing use of OT compounds in the chemical and biochemical fields, there has been little concern about their toxicity.…”

mentioning

confidence: 99%

Diphenyl Ditelluride‐Induced Cell Cycle Arrest and Apoptosis: A Relation with Topoisomerase I Inhibition

Jorge

Oliveira

Filippi-Chiela

et al. 2014

Basic Clin Pharma Tox

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The diphenyl ditelluride (DPDT) is a prototype for the development of new biologically active molecules. In previous studies, DPDT showed an elevated cytotoxicity in Chinese hamster fibroblast (V79) cells but the mechanisms for reduction of cell viability still remain unknown. DPDT showed mutagenic properties by induction of frameshift mutations in bacterium Salmonella typhimurium and yeast Saccharomyces cerevisiae. This organotelluride also induced DNA strand breaks in V79 cells. In this work, we investigated the mechanism of DPDT cytotoxicity by evaluating the effects of this compound on cell cycle progression, apoptosis induction and topoisomerase I inhibition. Significant decrease of V79 cell viability after DPDT treatment was revealed by MTT assay. Morphological analysis showed induction of apoptosis and necrosis by DPDT in V79 cells. An increase of caspase 3/7 activity confirmed apoptosis induction. The cell cycle analysis showed an increase in the percentage of V79 cells in S phase and sub-G1 phase. The yeast strain deficient in topoisomerase I (Topo I) showed higher tolerance to DPDT compared with the isogenic wild-type strain, suggesting that the interaction with this enzyme could be involved in DPDT toxicity. The sensitivity to DPDT found in top3Δ strain indicates that yeast topoisomerase 3 (Top3p) could participate in the repair of DNA lesions induced by the DPDT. We also demonstrated that DPDT inhibits human DNA topoisomerase I (Topo I) activity by DNA relaxation assay. Therefore, our results suggest that the DPDT-induced cell cycle arrest and reduction in cell viability could be attributed to interaction with topoisomerase I enzyme.

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Topical treatment for human papillomavirus-associated genital warts in humans with the novel tellurium immunomodulator AS101: assessment of its safety and efficacy

Abstract: AS101 15% w/w cream is an effective and safe, self-administered therapy used for the treatment of external vulval and perianal warts. The cream is applied topically twice daily for up to 16 weeks. A very low recurrence rate was reported.

Cited by 24 publications

References 20 publications

Involvement of the serotonergic system in the anxiolytic-like effect of 2-phenylethynyl butyltellurium in mice

Involvement of the serotonergic system in the anxiolytic-like effect of 2-phenylethynyl butyltellurium in mice

Tellurium Compound AS101 Ameliorates Experimental Autoimmune Encephalomyelitis by VLA-4 Inhibition and Suppression of Monocyte and T Cell Infiltration into the CNS

Diphenyl Ditelluride‐Induced Cell Cycle Arrest and Apoptosis: A Relation with Topoisomerase I Inhibition

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