Oxyresveratrol drives caspase-independent apoptosis-like cell death in MDA-MB-231 breast cancer cells through the induction of ROS

Sunilkumar, Damu; Drishya, G; Chandrasekharan, Aneesh; Shaji, Sanu K.; Bose, Chinchu; Jossart, Jennifer; Perry, J. Jefferson P.; Mishra, Nandita; Kumar, Geetha B.; Nair, Bipin G.

doi:10.1016/j.bcp.2019.113724

Cited by 33 publications

(18 citation statements)

References 57 publications

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“…ROS are important signalling molecules in cells, which participate in multiple signalling pathways. A recent report revealed that ROS participate in the induction of caspase-independent cell death in macrophages [33,34]. Moreover, ROS induce autophagy and apoptosis of tumour cells by inhibiting pathways such as PI3K/Akt and JNK, thereby suppressing the malignant phenotype of tumour cells [35,36].…”

Section: Discussionmentioning

confidence: 99%

BDH2 triggers ROS-induced cell death and autophagy by promoting Nrf2 ubiquitination in gastric cancer

Liu

Feng

et al. 2020

J Exp Clin Cancer Res

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Background: 3-Hydroxy butyrate dehydrogenase 2 (BDH2) is a short-chain dehydrogenase/reductase family member that plays a key role in the development and pathogenesis of human cancers. However, the role of BDH2 in gastric cancer (GC) remains largely unclear. Our study aimed to ascertain the regulatory mechanisms of BDH2 in GC, which could be used to develop new therapeutic strategies. Methods: Western blotting, immunohistochemistry, and RT-PCR were used to investigate the expression of BDH2 in GC specimens and cell lines. Its correlation with the clinicopathological characteristics and prognosis of GC patients was analysed. Functional assays, such as CCK-8 and TUNEL assays, transmission electron microscopy, and an in vivo tumour growth assay, were performed to examine the proliferation, apoptosis, and autophagy of GC cells. Related molecular mechanisms were clarified by luciferase reporter, coimmunoprecipitation, and ubiquitination assays. Results: BDH2 was markedly downregulated in GC tissues and cells, and the low expression of BDH2 was associated with poor survival of GC patients. Functionally, BDH2 overexpression significantly induced apoptosis and autophagy in vitro and in vivo. Mechanistically, BDH2 promoted Keap1 interaction with Nrf2 to increase the ubiquitination level of Nrf2. Ubiquitination/degradation of Nrf2 inhibited the activity of ARE to increase accumulation of reactive oxygen species (ROS), thereby inhibiting the phosphorylation levels of Akt Ser473 and mTOR Ser2448. Conclusions: Our study indicates that BDH2 is an important tumour suppressor in GC. BDH2 regulates intracellular ROS levels to mediate the PI3K/Akt/mTOR pathway through Keap1/Nrf2/ARE signalling, thereby inhibiting the growth of GC.

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Section: Discussionmentioning

confidence: 99%

BDH2 triggers ROS-induced cell death and autophagy by promoting Nrf2 ubiquitination in gastric cancer

Liu

Feng

et al. 2020

J Exp Clin Cancer Res

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“…Interestingly, ORV induced caspase-independent cell death in the highly chemo-resistant, triple-negative human breast cancer MDA-MB-231 cell line through the generation of ROS [ 211 ]. In a study with MCF-10A cells, ORV weakly inhibited NF-κB/DNA binding induced by the carcinogen TPA (12-O-tetradecanoylphorbol-13-acetate) [ 212 ].…”

Section: Biological and Pharmacological Activitiesmentioning

confidence: 99%

Oxyresveratrol: Sources, Productions, Biological Activities, Pharmacokinetics, and Delivery Systems

Likhitwitayawuid

2021

Molecules

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Oxyresveratrol has recently attracted much research attention due to its simple chemical structure and diverse therapeutic potentials. Previous reviews describe the chemistry and biological activities of this phytoalexin, but additional coverage and greater accessibility are still needed. The current review provides a more comprehensive summary, covering research from 1955 to the present year. Oxyresveratrol occurs in both gymnosperms and angiosperms. However, it has never been reported in plants in the subclass Sympetalae, and this point might be of both chemotaxonomic and biosynthetic importance. Oxyresveratrol can be easily obtained from plant materials by conventional methods, and several systems for both qualitative and quantitative analysis of oxyresveratrol contents in plant materials and plant products are available. Oxyresveratrol possesses diverse biological and pharmacological activities such as the inhibition of tyrosinase and melanogenesis, antioxidant and anti-inflammatory activities, and protective effects against neurological disorders and digestive ailments. However, the unfavorable pharmacokinetic properties of oxyresveratrol, including low water solubility and poor oral availability and stability, have posed challenges to its development as a useful therapeutic agent. Recently, several delivery systems have emerged, with promising outcomes that may improve chances for the clinical study of oxyresveratrol.

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“…Oxidative stress referred to the process of oxidative damage caused by the increase or elimination of oxygen free radicals in the body tissues or cells, resulting in the accumulation of reactive oxygen species in the body or cells [39]. ROS could attack biofilm unsaturated fatty acids to form lipid peroxides, and its product MDA was a harmful substance, which could be often used as an indicator to evaluate the strength of lipid peroxidation [40]. T-AOC was the reaction tissue cell enzymatic and an important indicator of the total antioxidant capacity of nonenzymatic systems [41].…”

Section: Elisa Detects Mda Production and T-aocmentioning

confidence: 99%

Superparamagnetic α-Fe2O3/Fe3O4 Heterogeneous Nanoparticles with Enhanced Biocompatibility

Wang

Liu

2021

Nanomaterials

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A novel type of magnetic α-Fe2O3/Fe3O4 heterogeneous nanoparticles was prepared via a facile solution combustion process with ferric nitrate and urea as raw materials, and they were characterized by XRD, SEM, TEM, and VSM techniques. The effects of the calcination temperature, the calcination time, the ratio of ferric nitrate and urea, and the heating rate on the relative content of Fe3O4 in the heterogeneous nanoparticles were investigated. The toxicity of α-Fe2O3/Fe3O4 heterogeneous nanoparticles to human hepatocytes L-02, the blood routine, and the histopathological section observation of mice were explored. The results showed that the ratio of ferric nitrate and urea was a key factor to affect the relative content of Fe3O4 in the heterogeneous nanoparticles. The calcination temperature and the calcination time had similar influences, and the corresponding calcination temperature and the calcination time were selected according to their own needs. The CCK8 results initially revealed that α-Fe2O3/Fe3O4 heterogeneous nanoparticles had no effect on cell viability when the concentration of the heterogeneous nanoparticles was less than 100 ng/mL, which suggested their excellent biocompatibility. At the same time, the tail vein administration concentration of 0.9 mg/kg had good biological safety.

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Oxyresveratrol drives caspase-independent apoptosis-like cell death in MDA-MB-231 breast cancer cells through the induction of ROS

Cited by 33 publications

References 57 publications

BDH2 triggers ROS-induced cell death and autophagy by promoting Nrf2 ubiquitination in gastric cancer

BDH2 triggers ROS-induced cell death and autophagy by promoting Nrf2 ubiquitination in gastric cancer

Oxyresveratrol: Sources, Productions, Biological Activities, Pharmacokinetics, and Delivery Systems

Superparamagnetic α-Fe2O3/Fe3O4 Heterogeneous Nanoparticles with Enhanced Biocompatibility

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