The heterocyclic compound Tempol inhibits the growth of cancer cells by interfering with glutamine metabolism

Ye, Shuangyan; Xu, Pengfei; Huang, Mengqiu; Chen, Xi; Zeng, Sisi; Wang, Qianli; Chen, Jianping; Li, Keyi; Gao, Wenwen; Liu, Ruiyuan; Liu, Jingxian; Shao, Yihao; Zhang, Hui; Xu, Yang; Zhang, Qianbing; Zhong, Zhuo; Wei, Zibo; Wang, Jiale; Hao, Bingtao; Huang, Wenhua; Liu, Qiuzhen

doi:10.1038/s41419-020-2499-8

Cited by 18 publications

(30 citation statements)

References 49 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…According to this mechanism, some authors include nitroxide among SOD-mimetic compounds. However, this remains a controversial proposal [ 24 , 176 , 188 , 220 , 318 ]. The discussion includes the classification of tempol and mito-tempo as SOD mimetics.…”

Section: Sod Sourcesmentioning

confidence: 99%

Superoxide Dismutase Administration: A Review of Proposed Human Uses

et al. 2021

View full text Add to dashboard Cite

Superoxide dismutases (SODs) are metalloenzymes that play a major role in antioxidant defense against oxidative stress in the body. SOD supplementation may therefore trigger the endogenous antioxidant machinery for the neutralization of free-radical excess and be used in a variety of pathological settings. This paper aimed to provide an extensive review of the possible uses of SODs in a range of pathological settings, as well as describe the current pitfalls and the delivery strategies that are in development to solve bioavailability issues. We carried out a PubMed query, using the keywords “SOD”, “SOD mimetics”, “SOD supplementation”, which included papers published in the English language, between 2012 and 2020, on the potential therapeutic applications of SODs, including detoxification strategies. As highlighted in this paper, it can be argued that the generic antioxidant effects of SODs are beneficial under all tested conditions, from ocular and cardiovascular diseases to neurodegenerative disorders and metabolic diseases, including diabetes and its complications and obesity. However, it must be underlined that clinical evidence for its efficacy is limited and consequently, this efficacy is currently far from being demonstrated.

show abstract

Section: Sod Sourcesmentioning

confidence: 99%

Superoxide Dismutase Administration: A Review of Proposed Human Uses

et al. 2021

View full text Add to dashboard Cite

show abstract

“…5B ). Moreover, the ROS scavenger Tempol ( 35 ) also partially reversed triclosan-induced increase of LDH release (0.5 and 1 mM; Fig. 5B ).…”

Section: Resultsmentioning

confidence: 80%

Triclosan induces ROS‑dependent cell death and autophagy in A375 melanoma cells

et al. 2020

View full text Add to dashboard Cite

Melanoma is a common type of cutaneous tumor, but current drug treatments do not satisfy clinical practice requirements. At present, mitochondrial uncoupling is an effective antitumor treatment. Triclosan, a common antimicrobial, also acts as a mitochondrial uncoupler. The aims of the present study were to investigate the effects of triclosan on melanoma cells and the underlying mechanisms. Mitochondrial membrane potential (MMP), mitochondrial morphology, mitochondrial reactive oxygen species (mito-ROS), intracellular superoxide anion and [Ca 2+ ] i were measured using confocal microscopy. It was found that triclosan application was associated with decreased A375 cell viability in a dose-and time-dependent manner and these effects may have cell specificity. Furthermore, triclosan induced MMP depolarization, ATP content decrease, mito-ROS and [Ca 2+ ] i level increases, excessive mitochondrial fission, AMP-activated protein kinase (AMPK) activation and STAT3 inhibition. Moreover, these aforementioned effects were reversed by acetylcysteine treatment. Triclosan acute treatment also induced mitochondrial swelling, which was reversed after AMPK-knockdown associated with [Ca 2+ ] i overload. Cell death was caused by STAT3 inhibition but not AMPK activation. Moreover, triclosan induced autophagy via the ROS/AMPK/p62/microtubule-associated protein 1A/1B-light chain 3 (LC3) signaling pathway, which may serve a role in feedback protection. Collectively, the present results suggested that triclosan increased mito-ROS production in melanoma cells, following induced cell death via the STAT3/Bcl-2 pathway and autophagy via the AMPK/p62/LC3 pathway.

show abstract

“…It is reported that millimole concentrations of Tempol or extended exposure to it increases ROS levels in juxtaglomerular cells 33 , breast cancer cells 35 , and ovarian cancer cells 34,36 . Results from the present study showed that ROS (DCF) levels were signi cantly increased in A549 cells treated with 0.…”

Section: Discussionmentioning

confidence: 99%

“…Treatment of Tempol at 1 ~ 5 mM inhibits cell growth and induces apoptosis in various cancer cells [33][34][35][36]41,45 . Likewise, 1 mM Tempol reduced the growth of scramble siRNA-transfected A549 and Calu-6 lung cancer cells, and Wi-38 VA-13 normal cells by about 55%, 50%, and 55% at 48 h, respectively.…”

Section: Discussionmentioning

confidence: 99%

“…(ATP) or NAD(P)H 46 . In addition, there are potentially harmful interactions between Tempol and enzyme complexes, which are inolved in glucose transport, glutamine metabolism and mitochondiral ATP production 21,24,34 . Therefore, further studies are needed on the difference in cellular ROS levels in lung cancer and normal cells following downregulation of TrxR1 and treatment with Tempol.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Tempol Differently Affects Cellular Redox Status and Antioxidant Enzymes in Various Lung-related Cells

park

2021

Preprint

View full text Add to dashboard Cite

Tempol (4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl) is a potential redox agent in cells. The present study investigated changes in cellular redox status [reactive oxygen species (ROS) and glutathione (GSH) levels] and in antioxidant enzymes, in Tempol-treated Calu-6 and A549 lung cancer cells, normal lung WI-38 VA-13 cells, and primary pulmonary fibroblasts. Results demonstrated that Tempol (0.5 ~ 4 mM) either increased or decreased general ROS levels in lung cancer and normal cells at 48 h and specifically increased O2•− levels in these cells. In addition, Tempol differentially altered the expression and activity of superoxide dismutase, catalase, and thioredoxin reductase1 (TrxR1) in A549, Calu-6, and WI-38 VA-13 cells. In particular, Tempol increased TrxR1 protein levels in these cells. Tempol at 1 mM inhibited the growth of lung cancer and normal cells by about 50% at 48 h but also significantly induced cell death, as evidenced by annexin V-positive cells. Furthermore, down-regulation of TrxR1 by siRNA somewhat affected the levels of cell growth inhibition and death as well as ROS in Tempol-treated cells. In addition, Tempol increased the numbers of GSH-depleted cells in both cancer cells and normal cells at 48h. In conclusion, Tempol differentially increased or decreased levels of ROS and various antioxidant enzymes in lung cancer and normal cells, and induced growth inhibition and death in all lung cells along with an increase in O2•− levels and GSH depletion.

show abstract

The heterocyclic compound Tempol inhibits the growth of cancer cells by interfering with glutamine metabolism

Cited by 18 publications

References 49 publications

Superoxide Dismutase Administration: A Review of Proposed Human Uses

Superoxide Dismutase Administration: A Review of Proposed Human Uses

Triclosan induces ROS‑dependent cell death and autophagy in A375 melanoma cells

Tempol Differently Affects Cellular Redox Status and Antioxidant Enzymes in Various Lung-related Cells

Contact Info

Product

Resources

About