A pentamethoxylated flavone from <i>Glycosmis ovoidea</i> promotes apoptosis through the intrinsic pathway and inhibits migration of <scp>MCF</scp>‐7 breast cancer cells

Anaya-Eugenio, Gerardo D.; Carcache, Peter J. Blanco; Ninh, Tran Ngoc; Ren, Yulin; Soejarto, Djaja D.; Kinghorn, A. Douglas

doi:10.1002/ptr.6930

Cited by 10 publications

(8 citation statements)

References 42 publications

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“…A natural flavone compound, 5,3′-dihydroxy-3,6,7,8,4′-pentamethoxyflavone (PMF), was reported to induce an intrinsic apoptotic pathway in MCF-7 cells via enhancing the expression of Bax, Cyt-C, and PARP-1, decreasing the Bcl-2 level. 96 Some other natural products, like Tracheloside (TCS) and Deoxypodophyllotoxin (DPT), could significantly inhibit the growth of CRC cells. 97 , 98 …”

Section: Crucial Signaling Pathways Of Rcd Subroutines In Cancermentioning

confidence: 99%

Regulated cell death (RCD) in cancer: key pathways and targeted therapies

Liao

Qin

et al. 2022

Sig Transduct Target Ther

305

154

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Regulated cell death (RCD), also well-known as programmed cell death (PCD), refers to the form of cell death that can be regulated by a variety of biomacromolecules, which is distinctive from accidental cell death (ACD). Accumulating evidence has revealed that RCD subroutines are the key features of tumorigenesis, which may ultimately lead to the establishment of different potential therapeutic strategies. Hitherto, targeting the subroutines of RCD with pharmacological small-molecule compounds has been emerging as a promising therapeutic avenue, which has rapidly progressed in many types of human cancers. Thus, in this review, we focus on summarizing not only the key apoptotic and autophagy-dependent cell death signaling pathways, but the crucial pathways of other RCD subroutines, including necroptosis, pyroptosis, ferroptosis, parthanatos, entosis, NETosis and lysosome-dependent cell death (LCD) in cancer. Moreover, we further discuss the current situation of several small-molecule compounds targeting the different RCD subroutines to improve cancer treatment, such as single-target, dual or multiple-target small-molecule compounds, drug combinations, and some new emerging therapeutic strategies that would together shed new light on future directions to attack cancer cell vulnerabilities with small-molecule drugs targeting RCD for therapeutic purposes.

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Section: Crucial Signaling Pathways Of Rcd Subroutines In Cancermentioning

confidence: 99%

Regulated cell death (RCD) in cancer: key pathways and targeted therapies

Liao

Qin

et al. 2022

Sig Transduct Target Ther

305

154

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“…Sideritoflavone inhibited JIMT 1 cell line migration but enhanced their motility by causing an increase in p65/NF-κΒ and activation of TGF-β signaling pathway (Sotillo et al, 2021). These findings can be compared to those of Anaya-Eugenio et al who also concluded that PMF inhibited migration of MCF-7 cells through reduced expression of p65/NF-κΒ (Anaya-Eugenio et al, 2021). Yao et al established that wogonoside exhibited antimetastatic effect through an array of mechanisms which included suppression of EMT in addition to inhibition of invasion and migration of TNF-α induced MDA-MB-231, MDA-MB-435, and BT-474 cells and TNF-α + TGF-β1-induced MCF7 cells (Yao et al, 2017).…”

Section: Inhibition Of Migration and Invasion (Anti-metastasis)mentioning

confidence: 70%

“…Cell viability using the MTT assay seemed to form a baseline against which a metabolite qualifies for further investigation. The studied flavonoids mainly displayed a dose and time-dependent effect on the variant breast cancer cell lines tested (Anaya-Eugenio et al, 2021;Attari et al, 2021;Go et al, 2018;Hallman et al, 2017;Hart et al, 2018;Hwang et al, 2020;Jia et al, 2018;Karimi et al, 2017;Li et al, 2017Li et al, , 2018Liang et al, 2021;Moradi et al, 2020;Qiu et al, 2019;Wang et al, 2021;Yu et al, 2018). The sensitivity of the flavonoids differed based on flavonoid type, concentration and cell line used.…”

Section: Cell Viabilitymentioning

confidence: 99%

“…Cell cycle arrest at G1, G2/M and S can eventually result in apoptosis of the cancerous cells (Lin et al, 2015). Flavonoids such as; xanthomirol, calycopterin, PMF, genistin, quercetin and baicalein were shown to arrest the BC cell cycle at G1 phase (Anaya-Eugenio et al, 2021;Attari et al, 2021;Hwang et al, 2020;Li et al, 2018;Yu et al, 2018). On the contrary, other flavonoids caused arrest of cell cycle at G2/M phase.…”

Section: Cell Cycle Arrestmentioning

confidence: 99%

“…The mechanisms involved included reduction in expression of antiapoptotic genes such as Bcl2, XIAP and increased expression of Bax, PARP 1, caspases 3, 7, 8, 9. Other mechanisms included increased mitochondrial oxidative stress, downregulation of mitochondrial membrane potential, inhibition of NF-κB, modulation of miR-200b/JAZF1 pathway and activation of PAX8-AS1-N/miR-17-5p/PTEN, CDKNIA,ZBTB4 regulation axis (Abbaszadeh et al, 2018;Anaya-Eugenio et al, 2021;Attari et al, 2021;Harrath et al, 2021;Hwang et al, 2020;Ko et al, 2020;Lee et al, 2020;Liang et al, 2021;Moradi et al, 2020;Pham et al, 2021;Qiu et al, 2019;Truong et al, 2021;Vrhovac Madunić et al, 2018;Wang et al, 2021;Xu et al, 2019b;Yu et al, 2018;Zhang et al, 2020;Zhu & Xue, 2019).…”

Section: Apoptosismentioning

confidence: 99%

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Molecular mechanisms of flavonoids and their modulatory effects against breast cancer: A scoping review

Murithi

Wambugu²,

Nyanjom

et al. 2022

F1000Res

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Background: Breast cancer is the most prevalent malignancy among women. It is a disease whose incidence and mortality rates are on the upsurge globally. Debilitating effects, cost and resistance to available chemotherapeutic interventions render them unideal. Dietary phytochemicals have been shown to have preventive and therapeutic effects. Research continues to affirm the role of flavonoids as potential chemotherapeutic agents in combating the disease. Understanding modulation of key cellular signalling pathways by flavonoids presents promising molecular targets that may be leveraged to develop better chemotherapeutic agents for breast cancer. Methods: To describe the in vitro and in vivo modulatory effects of flavonoids on molecular anti-cancer mechanisms we searched three databases. We included original articles describing modulation of cell signalling processes such as; cell cycle, apoptosis, autophagy, angiogenesis, invasion and migration which are involved in tumorigenesis. The search guidelines such as; year of publication, search strategy, study design and language informed article selection. Results: Thirty-six articles were reviewed. Modulatory effects of six subclasses of flavonoids on breast cancer tumorigenic pathways were reported. The effects included enhanced apoptosis, attenuation of; angiogenesis, cell cycle, invasion, migration and metastasis. For instance, pectolinarigenin inhibited signal transducer and activator of transcription 3 (stat3) signalling pathway in triple negative breast cancer. Whereas, sideritoflavone caused cell cycle arrest and inhibited migration in trastuzumab resistant breast cancer cells. Additionally, quercetin and ampelopsin inhibited stemness features in triple negative breast cancer cells. Conclusion: Evidently flavonoids showed significant modulatory effects on cellular signalling pathways crucial for breast cancer progression. The ability of flavonoids to act on a wide range of mechanisms as well as on aggressive breast cancer types presents an array of hope. We recommend that further studies be done to ascertain the applicability of these compounds in treatment of breast cancers.

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Cell plasticity modulation by flavonoids in resistant breast carcinoma targeting the nuclear factor kappa B signaling

Kubatka,

Koklesova,

Mazurakova

et al. 2023

Cancer Metastasis Rev

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Cancer cell plasticity plays a crucial role in tumor initiation, progression, and metastasis and is implicated in the multiple cancer defense mechanisms associated with therapy resistance and therapy evasion. Cancer resistance represents one of the significant obstacles in the clinical management of cancer. Some reversal chemosensitizing agents have been developed to resolve this serious clinical problem, but they have not yet been proven applicable in oncological practice. Activated nuclear factor kappa B (NF-κB) is a frequently observed biomarker in chemoresistant breast cancer (BC). Therefore, it denotes an attractive cellular target to mitigate cancer resistance. We summarize that flavonoids represent an essential class of phytochemicals that act as significant regulators of NF-κB signaling and negatively affect the fundamental cellular processes contributing to acquired cell plasticity and drug resistance. In this regard, flavokawain A, icariin, alpinetin, genistein, wogonin, apigenin, oroxylin A, xanthohumol, EGCG, hesperidin, naringenin, orientin, luteolin, delphinidin, fisetin, norwogonin, curcumin, cardamonin, methyl gallate and catechin-3-O-gallate, ampelopsin, puerarin, hyperoside, baicalein, paratocarpin E, and kaempferol and also synthetic flavonoids such as LFG-500 and 5,3′-dihydroxy-3,6,7,8,4′-pentamethoxyflavone have been reported to specifically interfere with the NF-κB pathway with complex signaling consequences in BC cells and could be potentially crucial in re-sensitizing unresponsive BC cases. The targeting NF-κB by above-mentioned flavonoids includes the modification of tumor microenvironment and epithelial-mesenchymal transition, growth factor receptor regulations, and modulations of specific pathways such as PI3K/AKT, MAP kinase/ERK, and Janus kinase/signal transduction in BC cells. Besides that, NF-κB signaling in BC cells modulated by flavonoids has also involved the regulation of ATP-binding cassette transporters, apoptosis, autophagy, cell cycle, and changes in the activity of cancer stem cells, oncogenes, or controlling of gene repair. The evaluation of conventional therapies in combination with plasticity-regulating/sensitizing agents offers new opportunities to make significant progress towards a complete cure for cancer. Graphical abstract

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A pentamethoxylated flavone from Glycosmis ovoidea promotes apoptosis through the intrinsic pathway and inhibits migration of MCF‐7 breast cancer cells

Cited by 10 publications

References 42 publications

Regulated cell death (RCD) in cancer: key pathways and targeted therapies

Regulated cell death (RCD) in cancer: key pathways and targeted therapies

Molecular mechanisms of flavonoids and their modulatory effects against breast cancer: A scoping review

Cell plasticity modulation by flavonoids in resistant breast carcinoma targeting the nuclear factor kappa B signaling

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