Anticancer effect of nor-wogonin (5, 7, 8-trihydroxyflavone) on human triple-negative breast cancer cells via downregulation of TAK1, NF-κB, and STAT3

El-Hafeez, Amer Ali Abd; Khalifa, Hazim O.; Mahdy, Elham A.M.; Sharma, Vikas; Hosoi, Toru; Ghosh, Pradipta; Ozawa, Koichiro; Montano, Monica M.; Fujimura, Takashi; Ibrahim, Akram; Abdel‐Hamid, Mohamed; Pack, Seung Pil; Shouman, Samia A.; Kawamoto, Seiji

doi:10.1016/j.pharep.2019.01.001

Cited by 32 publications

(22 citation statements)

References 44 publications

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“…Similarly, (5, 7, 8-trihydroxyflavone (NOR-wogonin) is a polyhydroxyflavone with antitumor activity. It can significantly inhibit the proliferation of TNBC cell lines (MDA-MB-231, BT-549, HCC70, and HCC1806) compared with non-tumorigenic BC lines (MCF-10A and AG11132) through downregulating the expression of CDK1 [159]. Moreover, Galangin, another plant anticancer compound, inhibits the survival of MCF-7 cells and induces apoptosis by downregulating CDK1, CDK2, and CDK4, leading to cell-cycle arrest [160].…”

Section: The Novel Cdk Inhibitors In Bcmentioning

confidence: 99%

The Roles of Cyclin-Dependent Kinases in Cell-Cycle Progression and Therapeutic Strategies in Human Breast Cancer

Ding

Cao

Lin

et al. 2020

IJMS

383

216

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Cyclin-dependent kinases (CDKs) are serine/threonine kinases whose catalytic activities are regulated by interactions with cyclins and CDK inhibitors (CKIs). CDKs are key regulatory enzymes involved in cell proliferation through regulating cell-cycle checkpoints and transcriptional events in response to extracellular and intracellular signals. Not surprisingly, the dysregulation of CDKs is a hallmark of cancers, and inhibition of specific members is considered an attractive target in cancer therapy. In breast cancer (BC), dual CDK4/6 inhibitors, palbociclib, ribociclib, and abemaciclib, combined with other agents, were approved by the Food and Drug Administration (FDA) recently for the treatment of hormone receptor positive (HR+) advanced or metastatic breast cancer (A/MBC), as well as other sub-types of breast cancer. Furthermore, ongoing studies identified more selective CDK inhibitors as promising clinical targets. In this review, we focus on the roles of CDKs in driving cell-cycle progression, cell-cycle checkpoints, and transcriptional regulation, a highlight of dysregulated CDK activation in BC. We also discuss the most relevant CDK inhibitors currently in clinical BC trials, with special emphasis on CDK4/6 inhibitors used for the treatment of estrogen receptor-positive (ER+)/human epidermal growth factor 2-negative (HER2−) M/ABC patients, as well as more emerging precise therapeutic strategies, such as combination therapies and microRNA (miRNA) therapy.

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Section: The Novel Cdk Inhibitors In Bcmentioning

confidence: 99%

The Roles of Cyclin-Dependent Kinases in Cell-Cycle Progression and Therapeutic Strategies in Human Breast Cancer

Ding

Cao

Lin

et al. 2020

IJMS

383

216

View full text Add to dashboard Cite

show abstract

“…Both compounds have also exerted their anticancer activities in TNBC models in vitro and in vivo [104, 105]. Moreover, nor-wogonin was found to inhibit the expression of transforming growth factor β-activated kinase 1 (TAK1), therefore dephosphorylating STAT3 without affecting its total expression level [106]. The dopamine receptor D2 (DRD2)-targeting drug thioridazine inhibits TNBC cell self-renewal through reducing DRD2-mediated STAT3 activation [107].…”

Section: Targeting Stat3 For Tnbc Prevention and Therapymentioning

confidence: 99%

STAT3 as a potential therapeutic target in triple negative breast cancer: a systematic review

Qin

Li²,

Zhang³

et al. 2019

J Exp Clin Cancer Res

286

187

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Triple negative breast cancer (TNBC), which is typically lack of expression of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2), represents the most aggressive and mortal subtype of breast cancer. Currently, only a few treatment options are available for TNBC due to the absence of molecular targets, which underscores the need for developing novel therapeutic and preventive approaches for this disease. Recent evidence from clinical trials and preclinical studies has demonstrated a pivotal role of signal transducer and activator of transcription 3 (STAT3) in the initiation, progression, metastasis, and immune evasion of TNBC. STAT3 is overexpressed and constitutively activated in TNBC cells and contributes to cell survival, proliferation, cell cycle progression, anti-apoptosis, migration, invasion, angiogenesis, chemoresistance, immunosuppression, and stem cells self-renewal and differentiation by regulating the expression of its downstream target genes. STAT3 small molecule inhibitors have been developed and shown excellent anticancer activities in in vitro and in vivo models of TNBC. This review discusses the recent advances in the understanding of STAT3, with a focus on STAT3's oncogenic role in TNBC. The current targeting strategies and representative small molecule inhibitors of STAT3 are highlighted. We also propose potential strategies that can be further examined for developing more specific and effective inhibitors for TNBC prevention and therapy.

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“…Studies have revealed that norwogonin owns antioxidant [ 25 ], anticancer [ 26 , 27 ], antiviral [ 28 ] and antimicrobial activities [ 29 ] as well as inhibits the cyanide-stimulated production of ROS [ 30 ]. However, whether norwogonin has protective capacities against hypoxia-induced injury remains unknown.…”

Section: Introductionmentioning

confidence: 99%

Norwogonin attenuates hypoxia-induced oxidative stress and apoptosis in PC12 cells

Jing

Gao

Zhang

et al. 2021

BMC Complement Med Ther

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Background Norwogonin is a natural flavone with three phenolic hydroxyl groups in skeletal structure and has excellent antioxidant activity. However, the neuroprotective effect of norwogonin remains unclear. Here, we investigated the protective capacity of norwogonin against oxidative damage elicited by hypoxia in PC12 cells. Methods The cell viability and apoptosis were examined by MTT assay and Annexin V-FITC/PI staining, respectively. Reactive oxygen species (ROS) content was measured using DCFH-DA assay. Lactate dehydrogenase (LDH), malondialdehyde (MDA) and antioxidant enzyme levels were determined using commercial kits. The expression of related genes and proteins was measured by real-time quantitative PCR and Western blotting, respectively. Results We found that norwogonin alleviated hypoxia-induced injury in PC12 cells by increasing the cell viability, reducing LDH release, and ameliorating the changes of cell morphology. Norwogonin also acted as an antioxidant by scavenging ROS, reducing MDA production, maintaining the activities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx), and decreasing the expression levels of HIF-1α and VEGF. In addition, norwogonin prevented cell apoptosis via inhibiting the expression levels of caspase-3, cytochrome c and Bax, while increasing the expression levels of Bcl-2 and the ratio of Bcl-2/Bax. Conclusions Norwogonin attenuates hypoxia-induced injury in PC12 cells by quenching ROS, maintaining the activities of antioxidant enzymes, and inhibiting mitochondrial apoptosis pathway.

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Anticancer effect of nor-wogonin (5, 7, 8-trihydroxyflavone) on human triple-negative breast cancer cells via downregulation of TAK1, NF-κB, and STAT3

Cited by 32 publications

References 44 publications

The Roles of Cyclin-Dependent Kinases in Cell-Cycle Progression and Therapeutic Strategies in Human Breast Cancer

The Roles of Cyclin-Dependent Kinases in Cell-Cycle Progression and Therapeutic Strategies in Human Breast Cancer

STAT3 as a potential therapeutic target in triple negative breast cancer: a systematic review

Norwogonin attenuates hypoxia-induced oxidative stress and apoptosis in PC12 cells

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