Abstract:
:Autophagy modulation is a potential therapeutic strategy for breast cancer, and a previous study indicated that metformin exhibits significant anti-carcinogenic activity. However, the ability of metformin to induce autophagy and its role in breast cancer cell death remains unclear. In this study, we exposed MCF-7 cells to different concentrations of metformin (2.5, 5, and 10 mM) for 48 h, and metformin-induced significant apoptosis in the MCF-7 cells. The expression levels of CL-PARP (poly(ADP-ribose) polymerase 1) and the ratio of BAX to BCL-2 were significantly increased. In addition to apoptosis, we showed that metformin increased autophagic flux in MCF-7 cells, as evidenced by the upregulation of LC3-II and downregulation of P62/SQSTM1. Moreover, pharmacological or genetic blocking of autophagy increased metformin-induced apoptosis, indicating a cytoprotective role of autophagy in metformin-treated MCF-7 cells. Mechanistically, metformin-induced TFE3(Ser321) dephosphorylation activated TFE3 nuclear translocation and increased of TFE3 reporter activity, which contributed to lysosomal biogenesis and the expression of autophagy-related genes and, subsequently, initiated autophagy in MCF-7 cells. Importantly, we found that metformin triggered the generation of reactive oxygen species (ROS) in MCF-7 cells. Furthermore, N-acetyl-l-cysteine (NAC), a ROS scavenger, abrogated the effects of metformin on TFE3-dependent autophagy. Notably, TFE3 expression positively correlated with breast cancer development and poor prognosis in patients. Taken together, these data demonstrate that blocking ROS-TFE3-dependent autophagy to enhance the activity of metformin warrants further attention as a treatment strategy for breast cancer.
journal_name
Free Radic Resjournal_title
Free radical researchauthors
Tan M,Wu A,Liao N,Liu M,Guo Q,Yi J,Wang T,Huang Y,Qiu B,Zhou Wdoi
10.1080/10715762.2018.1485075subject
Has Abstractpub_date
2018-08-01 00:00:00pages
872-886issue
8eissn
1071-5762issn
1029-2470journal_volume
52pub_type
杂志文章abstract::The intestinal tract, known for its capability for self-renew, represents the first barrier of defence between the organism and its luminal environment. The thiol/disulfide redox systems comprising the glutathione/glutathione disulfide (GSH/GSSG), cysteine/cystine (Cys/CySS) and reduced and oxidized thioredoxin (Trx/T...
journal_title:Free radical research
pub_type: 杂志文章,评审
doi:10.3109/10715762.2011.611509
更新日期:2011-11-01 00:00:00
abstract::Amphotericin B has been the gold standard for the treatment of invasive mycosis for many years. Its resistance mechanisms are reported to be mainly related to the decrease of ergosterol content or the changes of cell wall. Previous study has shown that Saccharomyces cerevisiae strain lack of BSC2 was sensitive signifi...
journal_title:Free radical research
pub_type: 杂志文章
doi:10.1080/10715762.2020.1751151
更新日期:2020-04-01 00:00:00
abstract::Over the last decades, oxidative stress has been described as a deleterious phenomenon contributing to numerous noncommunicable diseases such as cardiovascular disease, diabetes, and cancers. As many authors ascribed the healthy effect of fruit and vegetable consumption mainly to their antioxidant contents, it has bee...
journal_title:Free radical research
pub_type: 杂志文章
doi:10.3109/10715762.2013.853877
更新日期:2013-12-01 00:00:00
abstract::It has been observed that H9c2 cardiac cells cultured in physiologic solutions exhibit delayed cell death after repeated medium replacements, of which the cause was the relatively mild osmotic challenges during the renewal of the culture medium. Interestingly, the cell damage was associated with altered intracellular ...
journal_title:Free radical research
pub_type: 杂志文章
doi:10.1080/10715760802691471
更新日期:2009-03-01 00:00:00
abstract::The antioxidative activities of hamamelitannin (2',5-di-O-galloyl-hamamelose), gallic acid and dl-alpha-tocopherol against lipid peroxyl radicals were evaluated in chemical and biological systems. The peroxyl radical scavenging activity was evaluated by electron spin resonance (ESR) method in which both spin-trapping ...
journal_title:Free radical research
pub_type: 杂志文章
doi:10.3109/10715769509147550
更新日期:1995-05-01 00:00:00
abstract::Paraquat is a synthetic bipyridylium salt widely used as herbicide and defoliant. Enzyme-catalyzed redoxcycling of paraquat generates oxygen radicals. The toxic, even lethal, effects of paraquat are due to free radical-mediated tissue injury. Ocular lesions, sometimes quite severe, have been observed following acciden...
journal_title:Free radical research
pub_type: 杂志文章
doi:10.3109/10715769509064020
更新日期:1995-07-01 00:00:00
abstract::Intake of antioxidants from the diet has been recognized to have beneficial health effects, but the potential benefit of taking antioxidants such as β-carotene as supplements is controversial. The aim of the present study was to evaluate the potential protective effects of a physiologically relevant concentration (2 μ...
journal_title:Free radical research
pub_type: 杂志文章
doi:10.3109/10715762.2013.815346
更新日期:2013-09-01 00:00:00
abstract::A zinc(II) phthalocyanine compound, tetra-alpha-(2,2,4-tirmethyl-3-pentoxy) Phthalocyanine Zinc (ZnPc(OR)(4)) was synthesized in this paper and this zinc (II) phthalocyanine compound was used as the photosensitizer in the photoinduced chemiluminescence (PCL) of lucigenin in N,N-dimethylformamide (DMF). The photoexcite...
journal_title:Free radical research
pub_type: 杂志文章
doi:10.1080/10715760701836839
更新日期:2008-02-01 00:00:00
abstract::The preventive effect of 20(S)-ginsenoside Rg(3) (20(S)-Rg(3)) on lipopolysaccharide (LPS)-induced oxidative tissue injury in rats was investigated in this study. The elevated serum nitrite/nitrate, glutamic oxaloacetic transaminase, glutamic pyruvic transaminase and creatinine levels in LPS-treated control rats were ...
journal_title:Free radical research
pub_type: 杂志文章
doi:10.1080/10715760701581740
更新日期:2007-10-01 00:00:00
abstract::Neopterin and its reduced form, 7,8 dihydroneopterin are pteridines released from macrophages and monocytes when stimulated with interferon gamma in vivo. The function of this response is unknown though there is an enormous amount of information available on the use of these compounds as clinical markers of monocyte/m...
journal_title:Free radical research
pub_type: 杂志文章
doi:10.3109/10715769509064027
更新日期:1995-08-01 00:00:00
abstract::Hyperthermia-induced apoptosis and its enhancement in the presence of a temperature-dependent free radical initiator, 2,2'-azobis (2-aminopropane) dihydrochloride (AAPH) were examined in human uterine cervical cancer cell lines, CaSki and HeLa. When both cell lines were treated with hyperthermia at 44 degrees C for 60...
journal_title:Free radical research
pub_type: 杂志文章
doi:10.1080/1071576031000088292
更新日期:2003-06-01 00:00:00
abstract::Non-small cell lung cancer (NSCLC) is the most common form of lung cancer. Radioresistance is a significant obstacle in NSCLC radiotherapy. Long non-coding RNA LINC00473 has been found to impact the radiotherapy in several malignant tumours. This study aimed to investigate the underlying role and mechanism of LINC0047...
journal_title:Free radical research
pub_type: 杂志文章
doi:10.1080/10715762.2020.1841900
更新日期:2020-10-01 00:00:00
abstract::Diosgenin possesses anti-inflammatory and anticancer properties. Activated neutrophils produce high concentrations of the superoxide anion which is involved in the pathophysiology of inflammation-related diseases and cancer. In the present study, the inhibitory effect and possible mechanisms of diosgenin on superoxide...
journal_title:Free radical research
pub_type: 杂志文章
doi:10.3109/10715762.2014.966705
更新日期:2014-12-01 00:00:00
abstract::Copper Fenton systems (Cu(II)/H2O2 and Cu(II)/Asc) inactivated the lipoamide reductase and enhanced the diaphorase activity of pig-heart lipoamide dehydrogenase (LADH). Cupric ions alone were less effective. As a result of Cu(II)/H2O2 treatment, the number of titrated thiols in LADH decreased from 6 to 1 per subunit. ...
journal_title:Free radical research
pub_type: 杂志文章
doi:10.3109/10715769509147543
更新日期:1995-03-01 00:00:00
abstract::It has been reported that haem oxygenase-1 (Hmox1) induction attenuates neointimal thickening. Here we further investigated the potential mechanisms regulating this important pathological process. We revealed that histone deacetylase 2 (HDAC2) was induced following Hmox1 induction under 1% oxygen treatment and this in...
journal_title:Free radical research
pub_type: 杂志文章
doi:10.1080/10715762.2018.1524578
更新日期:2018-10-01 00:00:00
abstract::Epidemiology studies have shown that consumption of fruits and vegetables is associated with the prevention of chronic diseases such as cancer and cardiovascular disease. Induction of cellular phase II detoxifying enzymes is associated with cancer preventive potential. Phenolsulfotransferases (PSTs) are traditionally ...
journal_title:Free radical research
pub_type: 杂志文章
doi:10.1080/10715760500150424
更新日期:2005-08-01 00:00:00
abstract::Hemopexin, a heme-binding serum glycoprotein, is thought to play an important role in the prevention of oxidative damage that may be catalysed by free heme. Through the use of EPR techniques, the generation of free radicals from organic hydroperoxides by heme and heme-hemopexin complexes, and the concomitant formation...
journal_title:Free radical research
pub_type: 杂志文章
doi:10.3109/10715769509065277
更新日期:1995-12-01 00:00:00
abstract::Retinal mitochondria become dysfunctional in diabetes and the production of superoxide radicals is increased; over-expression of MnSOD abrogates mitochondrial dysfunction and prevents the development of diabetic retinopathy. The mitochondrial DNA (mtDNA) is particularly prone to oxidative damage. The aim of this study...
journal_title:Free radical research
pub_type: 杂志文章
doi:10.3109/10715760903494168
更新日期:2010-03-01 00:00:00
abstract::The effects of inorganic phosphate (Pi), the main intracellular membrane permeable anion capable of altering mitochondrial pH gradients (Delta pH), were measured on mitochondrial H2O2 release. As expected, Pi decreased Delta pH and increased the electric membrane potential (Delta Psi). Mitochondrial H2O2 release was s...
journal_title:Free radical research
pub_type: 杂志文章
doi:10.1080/10715760400009258
更新日期:2004-10-01 00:00:00
abstract::Chronic obstructive pulmonary disease (COPD) is a major cause of mortality that has been associated with inflammation and oxidative stress. The purpose of the present case-control study was to determine the relationships between oxidative stress-related genetic variants and the risk and severity of COPD, as well as, t...
journal_title:Free radical research
pub_type: 杂志文章
doi:10.1080/10715762.2019.1572888
更新日期:2019-03-01 00:00:00
abstract::Oxidative reactions are thought to play a role in the inflammatory condition called fatty liver. It is unclear whether oxidized lipoprotein lipids or proteins are associated with future fatty liver. In the Cardiovascular Risk in Young Finns Study, we determined the circulating levels of LDL and HDL oxidized lipids and...
journal_title:Free radical research
pub_type: 杂志文章
doi:10.3109/10715762.2015.1133906
更新日期:2016-01-01 00:00:00
abstract::Myeloperoxidase (MPO), a major constituent of neutrophils, catalyzes the production of hypochlorous acid (HOCl) from hydrogen peroxide (H2O2) and chloride anion. We have previously reported that MPO-deficient (MPO(-/-)) neutrophils produce greater amount of macrophage inflammatory protein-2 (MIP-2) in vitro than do wi...
journal_title:Free radical research
pub_type: 杂志文章
doi:10.3109/10715762.2013.778990
更新日期:2013-05-01 00:00:00
abstract::The oxidative stress possibly resulting from an inherited respiratory chain (RC) deficiency was investigated in a series of human cultured skin fibroblasts presenting either ubiquinone depletion or isolated defect of the various RC complexes. Taken as an index for superoxide overproduction, a significant induction of ...
journal_title:Free radical research
pub_type: 杂志文章
doi:10.1080/10715760290021216
更新日期:2002-04-01 00:00:00
abstract::The role of oxidative stress in clinical cardiology is still controversial. The aims of the present study were to examine if minor ischaemic episodes as may occur during elective percutaneous coronary intervention (PCI) induce oxidative stress and, eventually, if oxygen stress correlates with myocardial injury. Thirty...
journal_title:Free radical research
pub_type: 杂志文章
doi:10.1080/10715760410001688339
更新日期:2004-05-01 00:00:00
abstract::The protecting ability of the Piper betle leaves-derived phenol, allylpyrocatechol (APC) against AAPH-induced membrane damage of human red blood cells (RBCs) was investigated. Compared to control, AAPH (50 mM) treatment resulted in significant hemolysis (55%, p < 0.01), associated with increased malondialdehyde (MDA) ...
journal_title:Free radical research
pub_type: 杂志文章
doi:10.3109/10715762.2013.816847
更新日期:2013-09-01 00:00:00
abstract::Neopterin and the reduced form, 7,8-dihydroneopterin (78NP) are pteridines released from macrophages when stimulated with gamma-interferon in vivo. The role of 78NP in inflammatory response is unknown though neopterin has been used clinically as a marker of immune cell activation, due to its very fluorescent nature. U...
journal_title:Free radical research
pub_type: 杂志文章
doi:10.1080/10715760100300121
更新日期:2001-02-01 00:00:00
abstract::Reactive oxygen species (ROS) are involved in the mechanism of photoaging and carcinogenesis. Skin is endowed with antioxidant enzymes including superoxide dismutases (SOD): cytosolic copper zinc SOD and mitochondrial manganese SOD. The aim of our study was to estimate the protective effect of manganese against oxidat...
journal_title:Free radical research
pub_type: 杂志文章
doi:10.3109/10715769509065255
更新日期:1995-10-01 00:00:00
abstract::The present study was designed to determine whether hydroxymethylglutaryl-CoA reductase inhibitors (statins) modulate the NO production via iNOS in adipocytes stimulated by lipopolysaccharide (L) and tumour necrosis factor-alpha (T). Well-differentiated 3T3-L1 adipocytes significantly produced NO by LT-treatment. Pre-...
journal_title:Free radical research
pub_type: 杂志文章
doi:10.1080/10715760701534368
更新日期:2007-09-01 00:00:00
abstract::Cigarette smoking is associated with increased oxidative stress and increased risk of degenerative disease. As the major lipophilic antioxidant, requirements for vitamin E may be higher in smokers due to increased utilisation. In this observational study we have compared vitamin E status in smokers and non-smokers usi...
journal_title:Free radical research
pub_type: 杂志文章
doi:10.1080/10715760410001715149
更新日期:2004-08-01 00:00:00
abstract::Oxidation of low density lipoprotein (LDL) has been implicated in the pathogenesis of atherosclerosis. The most common technique for measuring the oxidation of lipoproteins is the continuous measurement of the formation of conjugated diene at OD 234 nm. The concept of "lag time", derived from such measurements, has be...
journal_title:Free radical research
pub_type: 杂志文章,评审
doi:10.3109/10715769809065814
更新日期:1998-06-01 00:00:00