Metabolism, toxicity and anticancer activities of arsenic compounds

Han

Environmental Toxicology

et al. 2018

Arsenic trioxide (ATO; As O ) induces cell death in various cells via oxidative stress. Expose to chronic arsenic is involved in the development of vascular diseases. However, little is known about the cytotoxic effects of ATO on human normal vascular smooth muscle cells (VSMCs). Thus, in this study, we investigated the effects of ATO on cell growth and death in human pulmonary artery smooth muscle (HPASM) cells in relation to reactive oxygen species (ROS) and glutathione (GSH) levels. ATO treatment decreased the growth of HPASM cells with an IC of ∼30-50 μM at 24 h, and ATO induced HPASM cell death via apoptosis or necrosis dependent on the doses of it at this time. Treatment with 50 μM ATO did not increase ROS levels at the early time points, but it significantly increased mitochondrial O2•- levels at 24 h. ATO also induced GSH depletion in HPASM cells. N-acetyl cysteine (NAC; a well-known antioxidant) did not significantly affect apoptotic cell death, ROS levels, or GSH depletion in ATO-treated HPASM cells. However, l-buthionine sulfoximine (BSO; an inhibitor of GSH synthesis) intensified mitochondrial O2•- levels in ATO-treated HPASM cells, and significantly increased cell death and GSH depletion in these cells as well. In summary, we provided the first evidence that ATO inhibited the growth of HPASM cells, and induced apoptotic and/or necrotic cell death in these cells, accompanied by increases in mitochondrial O2•- level and GSH depletion.

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Arsenic trioxide induces growth inhibition and death in human pulmonary artery smooth muscle cells accompanied by mitochondrial increase and GSH depletion

Han

Environmental Toxicology

et al. 2018

“…In the arsenic biotransformation, a detoxification system that is present from bacteria to humans, first, the arsenate is converted into arsenite and then transformed into monomethylated, dimethylated, and trimethylated products . Thus, studies about the chemical form of arsenic, especially its transformation, allow to understand the biogeochemical cycling of this element in peculiar geo‐systems, and offer a molecular explanation of how exposed organisms tolerate arsenic in their environment.…”

Section: Discussionmentioning

confidence: 99%

Use of synchrotron radiation X‐ray fluorescence and X‐ray absorption spectroscopy to investigate bioaccumulation, molecular target, and biotransformation of volcanic elements

Lamela

Pérez

et al. 2018

X-Ray Spectrometry

Because environment pollutants have a strong impact on ecosystems, including human health, methods of their determination and mitigation have received special attention in recent years. Taking advantage of the wide range of data that can be obtained by synchrotron radiation X‐ray fluorescence spectroscopy (SRXRF) in the field of environmental sciences, different instrumental setups were used to study the biological fates of toxic elements in volcanic environments. The elemental composition of plants, algae, and bacteria in Copahue and Domuyo volcanoes from Argentinean Patagonia was determined by SRXRF and the volcanic elements Ti, Fe, and Zn were abundant in these organisms. Interestingly, a high As concentration was found in cyanobacteria (26.2 μg/g) living in As contaminated stream (250 μg/ml). Because arsenic is toxic and human carcinogen, element‐retention capacity, element‐protein associations, and arsenic metabolism in this As resistant organism were analyzed by SRXRF. A high capacity (100–95%) of Ti > Fe > Cr > Sr > Ni > Cu > Mn > Zn > As retention was found after aqueous/alcoholic extraction assisted by ultrasonication. The cyanobacterial proteins were separated by SDS‐PAGE, electro‐transferred to nitrocellulose, and mapped by SRXRF. Defined protein bands containing Ca, Ti, Mn, Fe, and/or Zn were observed. Their ability to metabolize arsenic was revealed by combining SRXRF and X‐ray absorption near edge spectroscopy and Dimethylarsenic was found. Based on results, we speculate that these cyanobacteria could be interesting candidates for water treatment. Finally, we conclude that SRXRF is a valuable tool to study the biological cycle of environmental pollutants, including their accumulation, molecular targets, and metabolism. The SRXRF may also assist in remediation researches.

“…Furthermore, organic arsenicals are generally thought to induce the apoptosis rather than cell re‐differentiation, which means organic arsenicals may carry out the anti‐cancer efficacy toward leukemia and lymphoma, as well as solid tumors. It has been reported that organic arsenical DAR can induce the cell cycle arrest, mitochondrial dysfunction, MAPK‐mediated SHP1‐dependent cell death or ROS‐mediated apoptosis . Although the signal pathways activated by DAR are diverse for the different cell lines, the influence on mitochondria is not neglected in all functional mechanisms.…”

Section: Introductionmentioning

confidence: 99%

Dual Inhibition of Pyruvate Dehydrogenase Complex and Respiratory Chain Complex Induces Apoptosis by a Mitochondria‐Targeted Fluorescent Organic Arsenical in vitro and in vivo

et al. 2020

Based on the potential therapeutic value in targeting mitochondria and the fluorophore tracing ability, a fluorescent mitochondria‐targeted organic arsenical PDT‐PAO‐F16 was fabricated, which not only visualized the cellular distribution, but also exerted anti‐cancer activity in vitro and in vivo via targeting pyruvate dehydrogenase complex (PDHC) and respiratory chain complexes in mitochondria. In details, PDT‐PAO‐F16 mainly accumulated into mitochondria within hours and suppressed the activity of PDHC resulting in the inhibition of ATP synthesis and thermogenesis disorder. Moreover, the suppression of respiratory chain complex I and IV accelerated the mitochondrial dysfunction leading to caspase family‐dependent apoptosis. In vivo, the acute promyelocytic leukemia was greatly alleviated in the PDT‐PAO‐F16 treated group in APL mice model. Our results demonstrated the organic arsenical precursor with fluorescence imaging and target‐anticancer efficacy is a promising anticancer drug.