Comparison of diarsenic oxide and tetraarsenic oxide on anticancer effects: Relation to the apoptosis molecular pathway

Chang, Hong-Seok; Bae, Su-Mi; Kwak, Sun-Young; Min, Hong-Ghi; Bae, IL-Ju; Lee, Young‐Joo; Shin, Jong-Chul; Kim, Chong‐Kook; Ahn, Woong‐Shick

doi:10.3892/ijo.30.5.1129

Cited by 16 publications

(19 citation statements)

References 18 publications

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“…Carbendazim has been reported for being associated in chromosomal aberrations [17]. It is also has been used in antimicrotubular drugs preparations, which interfere in the synthesis of DNA and assembly of microtubules and tubulin subunits during cell cycle or cellular development [18,19].…”

Section: Mtt Cell Viability Assaymentioning

confidence: 99%

In-vitro Assessment of Carbendazim and Copper oxychloride cytotoxicity on HaCaT and HepG2 human cell lines

2017

J App Biol Biotech

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The objective of present study was to evaluate the cytotoxic effect of two fungicides i.e. carbendazim and copper oxychloride on human cell lines HaCaT [keratinocyte] and HepG2 [hepatoma cell line]. The cytotoxic study was done by following the standard MTT [3-[4,5-dimethylthiazol-2-yl]-2,5-diphehyltetrazolium bromide] assay along with standard drug. The MTT assay results showed that these two fungicides showed concentration dependent cytotoxicity, upon incubation for 24 hours with concentration ranging 20-450 µg/ml and IC50 values were determined. The cell viability of HaCaT cells decreased from 100% to 35.86% with increase in carbendazim concentration 20-450 µg/ml. Whereas HepG2 cells were sensitive towards Carbendazim treatment with the decrease in viability up to 30.98% at 450 μg/ml. Copper oxychloride was more lethal, causing total cell death of HaCaT cells at 350 μg/ml, and HepG2 at 450 μg/ml and the present work correlate this toxicity caused by these two fungicides on human skin and liver. The study u nveils the cytotoxic effects of these fungicides on the skin as well as on the liver indicating the long term exposure to these compounds may lead to deleterious effects. Further study is needed on to identify the mechanism and pathway involved in the cytotoxic activity of these fungicides on HaCaT and HepG2 cell lines.

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Section: Mtt Cell Viability Assaymentioning

confidence: 99%

In-vitro Assessment of Carbendazim and Copper oxychloride cytotoxicity on HaCaT and HepG2 human cell lines

2017

J App Biol Biotech

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“…34 Tetraarsenic oxide is more effective at suppressing cancer cell growth in vitro and in vivo, and cells treated with TAO show more prominent features of apoptosis than those treated with ATO. 4 Furthermore, ATO has already shown the induction of autophagic cell death in malignant glioma cell lines at a low concentration as well as enhanced radiation-induced killing of a GBM cell line via increased intracellular ROS in vitro and in vivo in a xenograft mouse model. 18,31 Hence, we hypothesized that TAO could exert the same cytotoxic effect on malignant glioma at a lower concentration than ATO and could be more safely combined with radiation therapy, which takes at least 4-6 weeks of exposure to augment the cell-killing effect and/or prevent local invasion.…”

Section: 12mentioning

confidence: 99%

“…These researchers suggested that TAO more effectively inhibited cell growth and suppressed antiapoptotic factors at a lower concentration than did ATO. 4 According to reports about the inhibitory effect of ATO in solid tumors, a relatively high concentration of ATO is required to induce overt apoptotic cell death (IC 50 = 10-50 μM).…”

Section: Cytotoxic Effects Of Tao On Malignant Glioma Cell Linesmentioning

confidence: 99%

Tetraarsenic oxide–induced inhibition of malignant glioma cell invasion in vitro via a decrease in matrix metalloproteinase secretion and protein kinase B phosphorylation

Gwak

Park²,

Park³

et al. 2014

JNS

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Object. Local invasiveness of malignant glioma is a major reason for the failure of current treatments including surgery and radiation therapy. Tetraarsenic oxide (As 4 O 6 [TAO]) is a trivalent arsenic compound that has potential anticancer and antiangiogenic effects in selected cancer cell lines at a lower concentration than arsenic trioxide (As 2 O 3 [ATO]), which has been more widely tested in vitro and in vivo. The authors tried to determine the cytotoxic concentration of TAO in malignant glioma cell lines and whether TAO would show anti-invasive effects under conditions independent of cell death or apoptosis.Methods. The human phosphatase and tensin homolog (PTEN)-deficient malignant glioma cell lines U87MG, U251MG, and U373MG together with PTEN-functional LN428 were cultured with a range of micromolar concentrations of TAO. The invasiveness of the glioma cell lines was analyzed. The effect of TAO on matrix metalloproteinase (MMP) secretion and membrane type 1 (MT1)-MMP expression was measured using gelatin zymography and Western blot, respectively. Akt, or protein kinase B, activity, which is a downstream effector of PTEN, was assessed with a kinase assay using glycogen synthesis kinase-3b (GSK-3b) as a substrate and Western blotting of phosphorylated Akt.Results. Tetraarsenic oxide inhibited 50% of glioma cell proliferation at 6.3-12.2 μM. Subsequent experiments were performed under the same TAO concentrations and exposure times, avoiding the direct tumoricidal effect of TAO, which was confirmed with apoptosis markers. An invasion assay revealed a dose-dependent decrease in invasiveness under the influence of TAO. Both the gelatinolytic activity of MMP-2 and MT1-MMP expression decreased in a dose-dependent manner in all cell lines, which was in accordance with the invasion assay results. The TAO decreased kinase activity of Akt on GSK3b assay and inhibited Akt phosphorylation in a dose-dependent manner in all cell lines regardless of their PTEN status.Conclusions. These results showed that TAO effectively inhibits proliferation of glioblastoma cell lines and also exerts an anti-invasive effect via decreased MMP-2 secretion, decreased MT1-MMP expression, and the inhibition of Akt phosphorylation under conditions devoid of cytotoxicity. Further investigations using an in vivo model are needed to evaluate the potential role of TAO as an anti-invasive agent. (http://thejns.org/doi/abs/10.3171/2014.8.JNS131991) key worDS • glioblastoma • tetraarsenic oxide • invasion • matrix metalloproteinase • protein kinase B • oncologyAbbreviations used in this paper: AP-1 = activator protein-1; ATO = arsenic trioxide; BBB = blood-brain barrier; ECM = extracellular matrix; EGTA = ethylene glycol tetraacetic acid; FACS = flow-activated cell sorter; GBM = glioblastoma; GSK-3b = glycogen synthase kinase-3b; IC 50 = 50% inhibitory concentration; MMP = matrix metalloproteinase; MT1 = membrane type 1; PBS = phosphate-buffered saline; phospho-Akt = phosphorylated active Akt; PI3K = phosphoinositide 3-kinase; PTEN = phosphata...

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“…However, few studies regarding the anticancer effects of As 4 O 6 have been performed. Only a few reports showed that the anticancer effects of As 4 O 6 were more potent than those of As 2 O 3 in human cancer cells in vitro, and that signaling pathways of As 4 O 6 -induced cell death were different from those of As 2 O 3 (10). We previously demonstrated that As 4 O 6 induced both caspase-dependent apoptosis and autophagic cell death in human cancer cells (11).…”

Section: Introductionmentioning

confidence: 99%

Arsenic hexoxide enhances TNF-α-induced anticancer effects by inhibiting NF-κB activity at a safe dose in MCF-7 human breast cancer cells

et al. 2014

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Abstract. Arsenic hexoxide (As 4 O 6 ) has been used in Korean folk remedy for the treatment of cancer since the late 1980s. Evidence suggests that the anticancer effects of As 4 O 6 are different from those of As 2 O 3 . Tumor necrosis factor-α (TNF-α) is generally increased in advanced cancer and is closely related to cancer progression, although it has cancer-killing effects. The reason is that TNF-α activates nuclear factor-κB (NF-κB) that is involved in cell proliferation, invasion, drug resistance and metastasis. In the present study, we investigated the effects of As 4 O 6 on NF-κB activity, NF-κB-mediated cellular responses, and NF-κB-regulated gene expressions involved in metastasis at the concentrations of As 4 O 6 where no cytotoxicity was observed. As 4 O 6 suppressed NF-κB activation in both TNF-α-treated and control cells, and also suppressed IκB phosphorylation in a time-dependent manner, suggesting the suppression of NF-κB results, in part, from the inhibition of IκB degradation. We also confirmed the anti-NF-κB activity of As 4 O 6 with synergism with TNF-α by augmenting caspase-8 activation. As 4 O 6 also suppressed NF-κB activation induced by TNF-α, and some of the downstream NF-κB-regulated proteins involved in cancer proliferation, anti-apoptosis and metastasis. In conclusion, the present study demonstrated that As 4 O 6 has anticancer properties by inhibiting NF-κB activation and NF-κB-regulated proteins at least in part through the inhibition of IκB phosphorylation, especially in the conditions of advanced cancer where TNF-α is highly secreted.

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Comparison of diarsenic oxide and tetraarsenic oxide on anticancer effects: Relation to the apoptosis molecular pathway

Cited by 16 publications

References 18 publications

In-vitro Assessment of Carbendazim and Copper oxychloride cytotoxicity on HaCaT and HepG2 human cell lines

In-vitro Assessment of Carbendazim and Copper oxychloride cytotoxicity on HaCaT and HepG2 human cell lines

Tetraarsenic oxide–induced inhibition of malignant glioma cell invasion in vitro via a decrease in matrix metalloproteinase secretion and protein kinase B phosphorylation

Arsenic hexoxide enhances TNF-α-induced anticancer effects by inhibiting NF-κB activity at a safe dose in MCF-7 human breast cancer cells

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