Involvement of reactive oxygen species in 2-methoxyestradiol-induced apoptosis in human neuroblastoma cells

Zhang, Qi; Ma, Yan; Cheng, Y.-S. Robert; Li, Wenjie; Zhang, Zhenzhong; Chen, Shao-yu

doi:10.1016/j.canlet.2011.09.005

Cited by 43 publications

(23 citation statements)

References 49 publications

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“…Oxidative stress damages proteins, nucleic acids, and lipids, which leads to loss of membrane integrity, chromosomal instability, and mutations [ 31 ]. Treatment of neuroblastoma cells (SK-N-SH and SH-SY5Y cell lines) in vitro with 2ME2 resulted in significantly increased generation of reactive oxygen species (ROS) [ 32 ]. 2ME2 treatment was associated with a decreased mitochondrial membrane potential (in a dose-dependent manner), suggesting that ROS-induced mitochondrial injury mediated apoptosis induced by 2ME2 [ 32 ].…”

Section: Discussionmentioning

confidence: 99%

Exposure of Breast and Lung Cancer Cells to a Novel Estrone Analog Prior to Radiation Enhances Bcl-2-Mediated Cell Death

Nolte

Joubert

Lakier

et al. 2018

IJMS

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Following exposure of cells to gamma-radiation, a cascade of intracellular consequences may be observed in a semitemporal manner. This includes deoxyribonucleic acid (DNA) damage and reactive oxygen species (ROS) accumulation initially, with consequent signaling for DNA repair and facilitative regulation of the cell cycle. Failure to rectify the damage or ROS levels leads to induction of senescence or apoptosis. 2-Ethyl-3-O-sulfamoyl-estra-1,3,5(10),15-tetraen-17-ol (ESE-15-ol), a 2-methoxyestradiole analog designed in silico for superior pharmacokinetics, was investigated for its potential to enhance apoptotic signaling and decrease the long-term survival of cells exposed to radiation. Sequential early intracellular effects within radiation-treated MCF-7 breast- and A549 lung cancer cells pre-exposed to low-dose ESE-15-ol were investigated using various flow cytometric protocols, spectrophotometry, and microscopy. Long-term cellular survival and proliferation was examined using clonogenic studies, which demonstrated a significant decrease in the presensitized cells. Combination-treated cells exhibited increased superoxide formation, and decreased Bcl-2 expression and -phosphorylation. Induction of apoptosis and elevation of the sub-G1 phase was evident in the pre-exposed MCF-7 cells, although only minimally in the A549 cells at 48-h. These results indicate that low-dose ESE-15-ol may increase tumor response to radiation. Future studies will investigate the effect of ESE-15-ol pre-exposure on radiation-induced DNA damage and repair mechanisms.

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Section: Discussionmentioning

confidence: 99%

Exposure of Breast and Lung Cancer Cells to a Novel Estrone Analog Prior to Radiation Enhances Bcl-2-Mediated Cell Death

Nolte

Joubert

Lakier

et al. 2018

IJMS

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“…ROS-induced apoptosis also explains the beneficial effect of two analogs of nuclear receptor ligands in several types of cancer: 2-methoxyestradiol, a 17β-estradiol metabolite, and N-(4-hydroxyphenyl) retinamide, a synthetic analog of retinoic acid, have been shown to induce PCD in neuroblastoma and lung cancer cells, respectively 104,105 . Furthermore, platinum-based drugs elevate ROS levels that promote PCD; protocols for the administration of these compounds in combination with inhibitors of poly(ADP-ribose) polymerase (PARP), which is involved in the maintenance of DNA integrity, have been shown to arrest the growth of breast cancer cells, even in BRCA-deficient models 106,107 .…”

Section: Ros and Apoptosis (Type I Programmed Cell Death)mentioning

confidence: 99%

ROS in cancer therapy: the bright side of the moon

et al. 2020

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Reactive oxygen species (ROS) constitute a group of highly reactive molecules that have evolved as regulators of important signaling pathways. It is now well accepted that moderate levels of ROS are required for several cellular functions, including gene expression. The production of ROS is elevated in tumor cells as a consequence of increased metabolic rate, gene mutation and relative hypoxia, and excess ROS are quenched by increased antioxidant enzymatic and nonenzymatic pathways in the same cells. Moderate increases of ROS contribute to several pathologic conditions, among which are tumor promotion and progression, as they are involved in different signaling pathways and induce DNA mutation. However, ROS are also able to trigger programmed cell death (PCD). Our review will emphasize the molecular mechanisms useful for the development of therapeutic strategies that are based on modulating ROS levels to treat cancer. Specifically, we will report on the growing data that highlight the role of ROS generated by different metabolic pathways as Trojan horses to eliminate cancer cells.

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“…The ability of 2ME 2 to induce ROS or block its production seems to depend on the cell types. Thus, 2ME 2 induced ROS production to decrease cell viability in the MCF7 [38], nasopharyngeal carcinoma [39], ovarian cancer [40] or human neuroblastoma cells [41,42]. On the other hand, 2ME 2 blocked ROS production in non-cancer cells as the normal mouse spleen or swine granulosa cells [43,44].…”

Section: Reactive Oxygen Species (Ros)mentioning

confidence: 99%

Role of 2-methoxyestradiol, an Endogenous Estrogen Metabolite, in Health and Disease

Parada-Bustamante¹,

Valencia²,

Reuquén³

et al. 2015

MRMC

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Estradiol (E2) is a steroid hormone whose physiological actions are mainly mediated by its interaction with intracellular estrogen receptors (ER) leading to modification on the mRNA and protein synthesis in its target cells. However, estrogens can also activate several intracellular signal transduction cascades by non-genomic mechanisms. Estrogens must be inactivated and removed from blood through its conversion to soluble compounds with an apparent low estrogenic activity and decreased affinity for ER. In this context, 2-methoxyestradiol (2ME2) is generated by a sequential hydroxylation of E2 via the enzyme cytochrome P450 isoform 1A1 to produce 2-hydroxyestradiol (2OHE2) followed by a conjugation reaction catalyzed by the enzyme Catechol-O-Methyltransferase generating 2ME2 from 2OHE2. Recent evidence indicates that physiological concentration of 2ME2 may regulate several biological processes while high concentrations of this metabolite may induce pathophysiological alterations in several tissues. In the last years, 2ME2 has also been described as a promising anticancer drug although its cellular and molecular mechanisms are still being disclosed. Herein, we will review the available literature concerning the role of 2ME2 in health and disease. We will focus on to describing the intracellular mechanisms by which 2ME2 exerts its effects on reproductive and non-reproductive tissues. The promising anticancer effects of 2ME2 and its synthetic derivatives will also be discussed. Finally, a group of 2ME2-target genes that could be used as biomarkers of 2ME2 under physiological or pathophysiological conditions will be reviewed.

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Involvement of reactive oxygen species in 2-methoxyestradiol-induced apoptosis in human neuroblastoma cells

Cited by 43 publications

References 49 publications

Exposure of Breast and Lung Cancer Cells to a Novel Estrone Analog Prior to Radiation Enhances Bcl-2-Mediated Cell Death

Exposure of Breast and Lung Cancer Cells to a Novel Estrone Analog Prior to Radiation Enhances Bcl-2-Mediated Cell Death

ROS in cancer therapy: the bright side of the moon

Role of 2-methoxyestradiol, an Endogenous Estrogen Metabolite, in Health and Disease

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