Gold nanoparticles–conjugated quercetin induces apoptosis via inhibition of EGFR/PI3K/Akt–mediated pathway in breast cancer cell lines (MCF‐7 and MDA‐MB‐231)

Solaimuthu, Balakrishnan; Mukherjee, Sudip; Das, Sourav; Bhat, Firdous Ahmad; Paulraj, Raja Singh; Patra, Chitta Ranjan; Arunakaran, J.

doi:10.1002/cbf.3266

Cited by 154 publications

(87 citation statements)

References 64 publications

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“…We found that knockdown of WBP2 decreased the expression of EGFR, and key proteins involved in the EGFR/PI3K/Akt signaling pathway in TNBC cell lines. It is known that the EGFR/PI3K/Akt signaling pathway is the major cell survival pathway and plays an important role in cell growth, apoptosis, cell cycle progression, drug resistance, migration and invasion [27][28][29][30][31]. The EGFR signaling pathway has been reported to play an important role in the occurrence of TNBC, and the key proteins involved in this pathway may be effective therapeutic targets in TNBC [32][33][34][35].…”

Section: Discussionmentioning

confidence: 99%

WBP2 Downregulation Inhibits Proliferation by Blocking YAP Transcription and the EGFR/PI3K/Akt Signaling Pathway in Triple Negative Breast Cancer

Song¹,

Wu²,

Xie³

et al. 2018

Cell Physiol Biochem

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Background/Aims: Dysregulated expression of WW domain-binding protein 2 (WBP2) is associated with poor prognosis in ER+ breast cancer patients. However, its role in triple negative breast cancer (TNBC) has not been previously assessed. Therefore, we aimed to elucidate the functional mechanism of WBP2 in TNBC cells. Methods: qRT-PCR, western blotting, and immunohistochemical staining were used to evaluate WBP2 expression in TNBC patient tumors and cell lines. HCC1937 and MDA-MB-231 cells transiently transfected with WBP2 small interfering RNA (siRNA), miR-613 mimics, or miR-613 inhibitors were subject to assays for cell viability, apoptosis and cell cycle distribution. Co-immunoprecipitation, western blotting or qRT-PCR were employed to monitor changes in signaling pathway-related genes and proteins. Luciferase assays were performed to assess whether WBP2 is a direct target of miR-613. The effect of miR-613 on tumor growth was assessed in vivo using mouse xenograft models. Results: The expression of WBP2 was upregulated in TNBC tissues and cells. Expression of WBP2 was significantly correlated with Ki67 in TNBC patients. Knockdown of WBP2 inhibited cellular proliferation, promoted apoptosis, and induced cell cycle arrest of TNBC cells. miR-613 directly bound to the 3’-untranslated region (3’-UTR) of WBP2 and regulated the expression of WBP2. Moreover, miR-613 reduced the expression of WBP2 and suppressed tumor growth of TNBC cells in vivo. Knockdown of WBP2 inhibited YAP transcription and the EGFR/PI3K/Akt signaling pathway in TNBC cells, and these effects were reversed by inhibition of miR-613. Conclusion: WBP2 overexpression is associated with the poor prognosis of TNBC patients and the miR-613-WBP2 axis represses TNBC cell growth by inactivating YAP-mediated gene expression and the EGFR/PI3K/Akt signaling pathway.

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Section: Discussionmentioning

confidence: 99%

WBP2 Downregulation Inhibits Proliferation by Blocking YAP Transcription and the EGFR/PI3K/Akt Signaling Pathway in Triple Negative Breast Cancer

Song¹,

Wu²,

Xie³

et al. 2018

Cell Physiol Biochem

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“…Also, myricetin, other flavonoid from flavonols subgroup, in ovarian, breast, prostate, and glioblastoma (Boam, ; Jiao & Zhang, ; G. Wang, Wang, Tang, Du, & Li, ; Xu et al, ), and butein, flavonoid from chalcones subgroup, in leukemia, pancreatic, cervical, lung, colorectal, and breast (Bai, Ma, & Zhang, ; Cho, Woo, & Ko, ; Chua et al, ; Y. T. Huang et al, ; Ishikawa, Senba, & Mori, ; S. K. Jung et al, ) have promising anticancer effects. Additionally, well‐known flavonoid quercetin, a plant flavonol, induced apoptosis in gastric, bladder, glioblastoma, breast, lung, colon, ovarian, cervical, liver, and pancreatic cancer cells (Balakrishnan et al, ; H. Li & Chen, ; Lin et al, ; Liu et al, ; Nwaeburu, Abukiwan, Zhao, & Herr, ; Raja et al, ; Ren et al, ; Roomi, Kalinovsky, Rath, & Niedzwiecki, ; Tao et al, ; E. X. Wang et al, ).…”

Section: Flavonoids: Cancer Therapymentioning

confidence: 99%

Leukemia therapy by flavonoids: Future and involved mechanisms

Saraei

Marofi

Naimi

et al. 2018

Journal Cellular Physiology

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Flavonoids are a varied family of phytonutrients (plant chemicals) usually are detected in fruits and vegetables. In this big family, there exist more than 10,000 members that is separated into six chief subtypes: isoflavonols, flavonoenes, flavones, flavonols, anthocyanins, and chalcones. The natural compounds, such as fruits, have visible positive effects in regulating of survival involved signaling pathways that performance as the regulator of cell survival, growth, and proliferation. Researchers have established that commonly consumption up flavonoids decreases incidence and development risk of certain cancers, especially leukemia. Flavonoids have been able to induce apoptosis and stimulate cell cycle arrest in cancer cells via different pathways. Similarly, they have antiangiogenesis and antimetastasis capability, which were shown in wide ranges of cancer cells, particularly, leukemia. It seems that flavonoid because of their widespread approval, evident safety and low rate of side effects, have hopeful anticarcinogenic potential for leukemia therapy. Based on the last decade reports, the most important acting mechanisms of these natural compounds in leukemia cells are stimulating of apoptosis pathways by upregulation of caspase 3, 8, 9 and poly ADP‐ribose polymerase (PARP) and proapoptotic proteins, particularly Bax activation. As well, they can induce cell cycle arrest in target cells not only via increasing of activated levels of p21 and p53 but also by inhibition of cyclins and cyclin‐dependent kinases. Furthermore, attenuation of neclear factor‐κB and signal transducer and activator of transcription 3 activation, suppression of signaling pathway and downregulation of intracellular antiapoptotic proteins are other significant antileukemic function mechanism of flavonoids. Overall, it appears that flavonoids are promising and effective compounds in the field of leukemia therapy. In this review, we tried to accumulate and revise most promising flavonoids and finally declared their major working mechanisms in leukemia cells.

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“…Several groups of investigators have shown that numerous genes such as RASSF1A, MLH1, BRCA1, WIF-1, CDH1, MGMT, and APC are hypermethylated and can be used as biomarkers or indicators of prognosis. 14 Epigenetic processes can be reversed and this principle makes it a potential target for therapeutic intervention. 15 Several studies demonstrate that silenced TSGs in cervical cancer cells are reactivated by the use of epigenetic inhibitors.…”

Section: Introductionmentioning

confidence: 99%

Quercetin modifies 5′CpG promoter methylation and reactivates various tumor suppressor genes by modulating epigenetic marks in human cervical cancer cells

Sundaram¹,

Hussain²,

Haque

et al. 2019

J of Cellular Biochemistry

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The central role of epigenomic alterations in carcinogenesis has been widely acknowledged, particularly the impact of DNA methylation on gene expression across all stages of carcinogenesis is considered vital for both diagnostic and therapeutic strategies. Dietary phytochemicals hold great promise as safe anticancer agents and effective epigenetic modulators. This study was designed to investigate the potential of a phytochemical, quercetin as a modulator of the epigenetic pathways for anticancer strategies. Biochemical activity of DNA methyltransferases (DNMTs), histone deacetylases (HDACs), histone methyltransferases (HMTs), and global genomic DNA methylation was quantitated by an enzyme‐linked immunosorbent assay based assay in quercetin‐treated HeLa cells. Molecular docking studies were performed to predict the interaction of quercetin with DNMTs and HDACs. Quantitative methylation array was used to assess quercetin‐mediated alterations in the promoter methylation of selected tumor suppressor genes (TSGs). Quercetin induced modulation of chromatin modifiers including DNMTs, HDACs, histone acetyltransferases (HAT) and HMTs, and TSGs were assessed by quantitative reverse transcription PCR (qRT‐PCR). It was found that quercetin modulates the expression of various chromatin modifiers and decreases the activity of DNMTs, HDACs, and HMTs in a dose‐dependent manner. Molecular docking results suggest that quercetin could function as a competitive inhibitor by interacting with residues in the catalytic cavity of several DNMTs and HDACs. Quercetin downregulated global DNA methylation levels in a dose‐ and time‐dependent manner. The tested TSGs showed steep dose‐dependent decline in promoter methylation with the restoration of their expression. Our study provides an understanding of the quercetin's mechanism of action and will aid in its development as a candidate for epigenetic‐based anticancer therapy.

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Gold nanoparticles–conjugated quercetin induces apoptosis via inhibition of EGFR/PI3K/Akt–mediated pathway in breast cancer cell lines (MCF‐7 and MDA‐MB‐231)

Cited by 154 publications

References 64 publications

WBP2 Downregulation Inhibits Proliferation by Blocking YAP Transcription and the EGFR/PI3K/Akt Signaling Pathway in Triple Negative Breast Cancer

WBP2 Downregulation Inhibits Proliferation by Blocking YAP Transcription and the EGFR/PI3K/Akt Signaling Pathway in Triple Negative Breast Cancer

Leukemia therapy by flavonoids: Future and involved mechanisms

Quercetin modifies 5′CpG promoter methylation and reactivates various tumor suppressor genes by modulating epigenetic marks in human cervical cancer cells

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