The Roles of 4β-Hydroxywithanolide E from <i>Physalis peruviana</i> on the Nrf2-Anti-Oxidant System and the Cell Cycle in Breast Cancer Cells

Peng, Chieh Yu; You, Bang Jau; Lee, Chia-Lin; Wu, Yang Chang; Lin, Wen-Hsin; Lu, Te‐Ling; Chang, Fei; Lee, Hong Zin

doi:10.1142/s0192415x16500348

Cited by 25 publications

(15 citation statements)

References 36 publications

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“…The role of oxidative stress effect in 4βHWE‐induced ROS generation, cell cycle change, and cell death has been reported in breast cancer cells (MCF‐7) by NAC pretreatment. However, this breast cancer study did not consider selective killing and oxidative DNA damage.…”

Section: Discussionmentioning

confidence: 99%

4β‐Hydroxywithanolide E selectively induces oxidative DNA damage for selective killing of oral cancer cells

Tang

Huang

Wang

et al. 2017

Environmental Toxicology

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Reactive oxygen species (ROS) induction had been previously reported in 4β-hydroxywithanolide (4βHWE)-induced selective killing of oral cancer cells, but the mechanism involving ROS and the DNA damage effect remain unclear. This study explores the role of ROS and oxidative DNA damage of 4βHWE in the selective killing of oral cancer cells. Changes in cell viability, morphology, ROS, DNA double strand break (DSB) signaling (γH2AX foci in immunofluorescence and DSB signaling in western blotting), and oxidative DNA damage (8-oxo-2'deoxyguanosine [8-oxodG]) were detected in 4βHWE-treated oral cancer (Ca9-22) and/or normal (HGF-1) cells. 4βHWE decreased cell viability, changed cell morphology and induced ROS generation in oral cancer cells rather than oral normal cells, which were recovered by a free radical scavenger N-acetylcysteine (NAC). For immunofluorescence, 4βHWE also accumulated more of the DSB marker, γH2AX foci, in oral cancer cells than in oral normal cells. For western blotting, DSB signaling proteins such as γH2AX and MRN complex (MRE11, RAD50, and NBS1) were overexpressed in 4βHWE-treated oral cancer cells in different concentrations and treatment time. In the formamidopyrimidine-DNA glycolyase (Fpg)-based comet assay and 8-oxodG-based flow cytometry, the 8-oxodG expressions were higher in 4βHWE-treated oral cancer cells than in oral normal cells. All the 4βHWE-induced DSB and oxidative DNA damage to oral cancer cells were recovered by NAC pretreatment. Taken together, the 4βHWE selectively induced DSB and oxidative DNA damage for the ROS-mediated selective killing of oral cancer cells.

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Section: Discussionmentioning

confidence: 99%

4β‐Hydroxywithanolide E selectively induces oxidative DNA damage for selective killing of oral cancer cells

Tang

Huang

Wang

et al. 2017

Environmental Toxicology

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“…This leads to enhanced expression of several detoxifying enzymes such as NQO1 and GSTP that play a key role in chemoprevention and therapy of breast cancer by reducing the level of estrogen quinones involved in toxicity and breast carcinogenicity. Recently, Peng et al72 also demonstrated that 4β-hydroxywithanolide E, an active component of the extract of Physalis peruviana , a member of the Solanaceae group, plays an important role in ROS production and subsequent ataxia-telangiectasia mutated protein-mediated apoptosis of breast cancer MCF-7 cells which is correlated with the expression of Nrf2-dependent antioxidative defense enzymes including SOD, CAT, and the glutathione system 72. Accordingly, pretreatment with antioxidants GSH and NAC was capable of reversing the 4β-hydroxywithanolide E-induced ROS accumulation and apoptotic cell death in MCF-7 cells.…”

Section: Introductionmentioning

confidence: 99%

<p>Dissecting the prevention of estrogen-dependent breast carcinogenesis through Nrf2-dependent and independent mechanisms</p>

Giudice

Barbieri

Bimonte

et al. 2019

OTT

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Breast cancer is the most common malignancy among women worldwide. Various studies indicate that prolonged exposure to elevated levels of estrogens is associated with development of breast cancer. Both estrogen receptor-dependent and independent mechanisms can contribute to the carcinogenic effects of estrogens. Among them, the oxidative metabolism of estrogens plays a key role in the initiation of estradiol-induced breast cancer by generation of reactive estrogen quinones as well as the associated formation of oxygen free radicals. These genotoxic metabolites can react with DNA to form unstable DNA adducts which generate mutations leading to the initiation of breast cancer. A variety of endogenous and exogenous factors can alter estrogen homeostasis and generate genotoxic metabolites. The use of specific phytochemicals and dietary supplements can inhibit the risk of breast cancer not only by the modulation of several estrogen-activating enzymes (CYP19, CYP1B1) but also through the induction of various cytoprotective enzymes (eg, SOD3, NQO1, glutathione S-transferases, OGG-1, catechol- O -methyltransferases, CYP1B1A, etc.) that reestablish the homeostatic balance of estrogen metabolism via nuclear factor erythroid 2-related factor 2 (Nrf2)-dependent and independent mechanisms.

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“…In our previous study, the protein expression of Cdk2 also displays two bands at about 33 kDa. 4β-Hydroxywithanolide E induced a marked increase in the amount of upper band and a significant reduction in the amount of lower band in MCF-7 cells 56 . A G1-phase arrest of the cell cycle was observed when MCF-7 cells were incubated with 4β-hydroxywithanolide E for 24 h in our previous study 56 , whereas fenofibrate induced cell cycle S and G2/M arrest in this study.…”

Section: Discussionmentioning

confidence: 87%

“…4β-Hydroxywithanolide E induced a marked increase in the amount of upper band and a significant reduction in the amount of lower band in MCF-7 cells 56 . A G1-phase arrest of the cell cycle was observed when MCF-7 cells were incubated with 4β-hydroxywithanolide E for 24 h in our previous study 56 , whereas fenofibrate induced cell cycle S and G2/M arrest in this study. Therefore, we indicated that the protein expression of lower band of Cdk2 might play a key role in regulation of the transition from G1 to S phase and S phase progression.…”

Section: Discussionmentioning

confidence: 87%

Fenofibrate induces human hepatoma Hep3B cells apoptosis and necroptosis through inhibition of thioesterase domain of fatty acid synthase

You

Hour

Chen

et al. 2019

Sci Rep

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This study demonstrated that fenofibrate, a lipid-lowering drug, induced a significant time-dependent cytotoxicity of hepatoma Hep3B cells. Hep3B cells are significantly more sensitive to cell killing by fenofibrate than hepatoma HepG2, lung cancer CH27 and oral cancer HSC-3 cells. From the result of docking simulation, fenofibrate can bind excellently to the thioesterase domain of fatty acid synthase (FASN) binding site as orlistat, a FASN inhibitor, acts. The fenofibrate-induced cell cytotoxicity was protected by addition of palmitate, indicating that the cytotoxic effect of fenofibrate is due to starvation of Hep3B cells by inhibiting the formation of end product in the FASN reaction. Inhibition of lipid metabolism-related proteins expression, such as proteins containing thioesterase domain and fatty acid transport proteins, was involved in the fenofibrate-induced Hep3B cell death. Fenofibrate caused S and G2/M cell cycle arrest by inducing cyclin A/Cdk2 and reducing cyclin D1 and E protein levels in Hep3B cells. The anti-tumor roles of fenofibrate on Hep3B cells by inducing apoptosis and necroptosis were dependent on the expression of Bcl-2/caspase family members and RIP1/RIP3 proteins, respectively. These results suggest that fenofibrate has an anti-cancer effect in Hep3B cells and inhibition of lipid metabolism may be involved in fenofibrate-induced Hep3B cells apoptosis and necroptosis.

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The Roles of 4β-Hydroxywithanolide E from Physalis peruviana on the Nrf2-Anti-Oxidant System and the Cell Cycle in Breast Cancer Cells

Cited by 25 publications

References 36 publications

4β‐Hydroxywithanolide E selectively induces oxidative DNA damage for selective killing of oral cancer cells

4β‐Hydroxywithanolide E selectively induces oxidative DNA damage for selective killing of oral cancer cells

<p>Dissecting the prevention of estrogen-dependent breast carcinogenesis through Nrf2-dependent and independent mechanisms</p>

Fenofibrate induces human hepatoma Hep3B cells apoptosis and necroptosis through inhibition of thioesterase domain of fatty acid synthase

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