Arsenic trioxide inhibits growth of As4.1 juxtaglomerular cells via cell cycle arrest and caspase-independent apoptosis

Han, Yong Hwan; Kim, Sung Zoo; Kim, Suhn Hee; Park, Woo Hyun

doi:10.1152/ajprenal.00385.2006

Cited by 79 publications

(51 citation statements)

References 47 publications

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“…MMP (∆Ψ m ) levels were measured using a rhodamine 123 fluorescent dye (Ex/Em = 485 nm/535 nm; Sigma-Aldrich Chemical) as previously described (43). In brief, 1x10 6 Western blot analysis.…”

Section: Measurement Of Mmp (∆ψ M )mentioning

confidence: 99%

Arsenic trioxide induces human pulmonary fibroblast cell death via increasing ROS levels and GSH depletion

You

Park

2012

Oncology Reports

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Abstract. Arsenic trioxide (ATO; As 2 O 3 ) induces apoptotic cell death in various cancer cells including lung cancer via the induction of reactive oxygen species (ROS). However, little is known about the toxicological effects of ATO on normal primary lung cells. Here, we investigated the effects of N-acetyl cysteine (NAC) and vitamin C (well-known antioxidants) or L-buthionine sulfoximine (BSO; an inhibitor of GSH synthesis) on ATO-treated human pulmonary fibroblast (HPF) cells in relation to cell death, ROS and glutathione (GSH). ATO induced growth inhibition and death in HPF cells, accompanied by the loss of mitochondrial membrane potential (MMP; ∆Ψ m ). ATO increased ROS levels including O 2•-and GSH depleted cell numbers. NAC attenuated the growth inhibition, death and MMP (∆Ψ m ) loss in ATO-treated HPF cells and also decreased the ROS levels in these cells. However, vitamin C enhanced the growth inhibition, death, MMP (∆Ψ m ) loss and GSH depletion by ATO and even strongly increased mitochondrial O 2•-levels in ATO-treated HPF cells. BSO showed a strong increase in ROS levels in ATO-treated HPF cells and intensified the growth inhibition, cell death, MMP (∆Ψ m ) loss and GSH depletion. Moreover, superoxide dismutase (SOD2) or thioredoxin (TXN) siRNAs attenuated HPF cell death by ATO, which was not correlated with ROS and GSH level changes. In conclusion, ATO induced the growth inhibition and death of HPF cells, accompanied by increasing ROS levels and GSH depletion. NAC attenuated HPF cell death by ATO whereas vitamin C and BSO enhanced the death.

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Section: Measurement Of Mmp (∆ψ M )mentioning

confidence: 99%

Arsenic trioxide induces human pulmonary fibroblast cell death via increasing ROS levels and GSH depletion

You

Park

2012

Oncology Reports

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“…The MMP (Δae m ) levels were measured by the Rhodamine 123 fluorescent dye (Ex/Em = 485/535 nm), as previously described (33). In brief, 1x10 6 cells were incubated with AMA with or without NAC, BSO, DDC or AT for 72 h. They were washed twice with PBS and incubated with Rhodamine 123 (0.1 μg/ml; Sigma) at 37˚C for 30 min.…”

Section: Measurement Of Mitochondrial Membrane Potential (Mmp) (δAe M )mentioning

confidence: 99%

The effects of N-acetyl cysteine, buthionine sulfoximine, diethyldithiocarbamate or 3-amino-1,2,4-triazole on antimycin A-treated Calu-6 lung cells in relation to cell growth, reactive oxygen species and glutathione

Park¹

2009

Oncol Rep

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Abstract. Antimycin A (AMA) inhibits mitochondrial electron transport between cytochrome b and c. We recently demonstrated that AMA inhibits the growth of lung cancer Calu-6 cells and the changes of reactive oxygen species (ROS) and glutathione (GSH) levels affect apoptosis in Calu-6 cells. Here, we examined the effects of N-acetylcysteine (NAC, a well known antioxidant), L-buthionine sulfoximine (BSO, an inhibitor of GSH synthesis), diethyldithiocarbamate (DDC, an inhibitor of Cu, Zn-SOD) or 3-amino-1,2,4-triazole (AT, an inhibitor of catalase) on AMAtreated Calu-6 cells in relation to cell death, ROS and GSH levels. Treatment with AMA induced cell growth inhibition, apoptosis and the loss of mitochondrial membrane potential (MMP) (Δae m ) in Calu-6 cells. While the intracellular ROS level was decreased in 50 μM AMA-treated Calu-6 cells, O 2•-levels among ROS were significantly increased. AMA also induced GSH depletion in Calu-6 cells. Treatment with NAC showed decreasing effect on O 2•-levels in AMA-treated cells preventing apoptosis, MMP (Δae m ) loss and GSH depletion in these cells. BSO significantly increased GSH depletion and apoptosis in AMA-treated cells. While both DDC and AT increased ROS levels in AMA-treated Calu-6 cells, only DDC intensified GSH depletion and apoptosis. BSO and AT increased the ROS level in Calu-6 control cells, but these agents did not induce apoptosis and GSH depletion. In conclusion, our results suggest that GSH depletion rather than ROS level in AMA-treated Calu-6 cells is more tightly related to apoptosis.

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“…MMP (∆ψ m ) levels were measured using Rhodamine 123 fluorescent dye (Ex/Em = 485 nm/535 nm; Sigma) as previously described (23). in brief, 1x10 6 cells in a 60-mm culture dish (nunc) were incubated with Ga and/or each MaPK inhibitor for 24 h. cells were washed twice with PBS and incubated with rhodamine 123 (0.1 µg/ml) at 37˚C for 30 min.…”

Section: Measurement Of Mmp (∆ψ M )mentioning

confidence: 99%

The MEK inhibitor PD98059 attenuates growth inhibition and death in gallic acid-treated Calu-6 lung cancer cells by preventing glutathione depletion

Han

Moon²,

You³

et al. 2010

Mol Med Rep

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Abstract. Gallic acid (Ga) is widely distributed in various plants and foods and has various biological effects. in this study, we investigated the effects of mitogen-activated protein kinase (MeK, JnK or p38) inhibitors on Ga-induced calu-6 lung cancer cell death in relation to reactive oxygen species (roS) and glutathione (GSH) levels. Ga inhibited the growth of calu-6 cells and induced apoptosis and/or necrosis accompanied by the loss of mitochondrial membrane potential (MMP; ∆ψ m ). roS levels and the number of GSH-depleted cells were observed to be increased at 24 h. MeK inhibitor suppressed cell growth inhibition, death, MMP (∆ψ m ) loss and GSH depletion induced by Ga, but failed to suppress the increase in roS levels. JnK inhibitor also somewhat suppressed cell growth inhibition, MMP (∆ψ m ) loss and GSH depletion induced by Ga, and limited the increase in roS levels. By contrast, p38 inhibitor mildly enhanced Ga-induced cell growth inhibition, MMP (∆ψ m ) loss and the increase in roS levels. in conclusion, MeK inhibitor suppressed Ga-induced cell growth inhibition and death in calu-6 cells. This was related to the prevention of GSH depletion. IntroductionGallic acid (Ga; 3,4,5-triphydroxyl-benzoic acid) is a polyhydroxylphenolic compound that is widely distributed in various plants, fruits and other foods (1), and is very well absorbed by humans (2). Various biological effects of Ga have been reported, including anti-bacterial (3), anti-viral (4) and anti-inflammatory activities (5). The major point of interest in Ga is related to its anti-cancer activity, which has been reported in various cancer cells, including prostate (6), lung (7,8), gastric, colon, breast, cervical and esophageal cancer (9). apoptosis induced by Ga is associated with oxidative stress derived from reactive oxygen species (roS), mitochondrial dysfunction and an increase in intracellular ca 2+ levels (10,11). controversially, Ga has been suggested to have both pro-oxidant and antioxidant properties depending on iron or H 2 o 2 levels in medium and plasma (12,13).There are currently three well-known mitogen-activated protein kinases (MaPKs): extracellular signal regulated kinase (erK1/2), c-Jun n-terminal kinase/stress-activated protein kinase (JnK/SaPK) and p38 kinase (14). each MaP kinase pathway has relatively different upstream activators and specific substrates (15). Multiple lines of evidence demonstrate that JnK and p38 are strongly activated by roS or by a mild oxidative shift in the intracellular thiol/disulfide redox state, leading to apoptosis (16,17). roS are also known to induce erK phosphorylation and to activate the erK pathway (18). in most instances, erK activation has a pro-survival rather than a pro-apoptotic effect (19). Since variations in the level of roS and differences in the function of MAPKs as influenced by ROS may have opposite effects in even the same type of cells, the relationship between roS and MaPKs in terms of cell survival or cell death signaling requires further clarification.understanding the tox...

show abstract

Arsenic trioxide inhibits growth of As4.1 juxtaglomerular cells via cell cycle arrest and caspase-independent apoptosis

Cited by 79 publications

References 47 publications

Arsenic trioxide induces human pulmonary fibroblast cell death via increasing ROS levels and GSH depletion

Arsenic trioxide induces human pulmonary fibroblast cell death via increasing ROS levels and GSH depletion

The effects of N-acetyl cysteine, buthionine sulfoximine, diethyldithiocarbamate or 3-amino-1,2,4-triazole on antimycin A-treated Calu-6 lung cells in relation to cell growth, reactive oxygen species and glutathione

The MEK inhibitor PD98059 attenuates growth inhibition and death in gallic acid-treated Calu-6 lung cancer cells by preventing glutathione depletion

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