Naringenin has a chemoprotective effect in MDA‑MB‑231 breast cancer cells via inhibition of caspase‑3 and ‑9 activities

Wang, Rui; Wang, Junhai; Dong, Tianfu; Shen, Jun; Gao, Xitao; Zhou, Jun

doi:10.3892/ol.2018.9704

Cited by 27 publications

(23 citation statements)

References 30 publications

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“…The present study was done using the MCF-7 breast cancer cell line, which is a luminal subtype and has wild-type p53. In previous studies, naringenin exhibited cytotoxicity on different subtypes of breast cancer, including luminal, HER2+, and triple-negative breast cancer and it showed anticancer activity in triple-negative breast cancer cells 4 T1 ( Qin et al, 2011 ) and MDA-MB-231 ( Filho et al, 2014 , Wang et al, 2019 ). Naringenin also exhibited cytotoxicity in MCF-7 breast cancer cells ( Eanes and Patel, 2016 , Xu et al, 2018 ) and HER2 positive breast cancer cells ( Chandrika et al, 2016 ).…”

Section: Discussionmentioning

confidence: 98%

Identification of potential therapeutic target of naringenin in breast cancer stem cells inhibition by bioinformatics and in vitro studies

Hermawan

Ikawati

Jenie

et al. 2021

Saudi Pharmaceutical Journal

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Cancer therapy is a strategic measure in inhibiting breast cancer stem cell (BCSC) pathways. Naringenin, a citrus flavonoid, was found to increase breast cancer cells’ sensitivity to chemotherapeutic agents. Bioinformatics study and 3D tumorsphere in vitro modeling in breast cancer (mammosphere) were used in this study, which aims to explore the potential therapeutic targets of naringenin (PTTNs) in inhibiting BCSCs. Bioinformatic analyses identified direct target proteins (DTPs), indirect target proteins (ITPs), naringenin-mediated proteins (NMPs), BCSC regulatory genes, and PTTNs. The PTTNs were further analyzed for gene ontology, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment, protein–protein interaction (PPI) networks, and hub protein selection. Mammospheres were cultured in serum-free media. The effects of naringenin were measured by MTT-based cytotoxicity, mammosphere forming potential (MFP), colony formation, scratch wound-healing assay, and flow cytometry-based cell cycle analyses and apoptosis assays. Gene expression analysis was performed using real-time quantitative polymerase chain reaction (q-RT PCR). Bioinformatics analysis revealed p53 and estrogen receptor alpha (ERα) as PTTNs, and KEGG pathway enrichment analysis revealed that TGF-ß and Wnt/ß-catenin pathways are regulated by PTTNs. Naringenin demonstrated cytotoxicity and inhibited mammosphere and colony formation, migration, and epithelial to mesenchymal transition in the mammosphere. The mRNA of tumor suppressors P53 and ERα were downregulated in the mammosphere, but were significantly upregulated upon naringenin treatment. By modulating the P53 and ERα mRNA, naringenin has the potential of inhibiting BCSCs. Further studies on the molecular mechanism and formulation of naringenin in BCSCs would be beneficial for its development as a BCSC-targeting drug.

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Section: Discussionmentioning

confidence: 98%

Identification of potential therapeutic target of naringenin in breast cancer stem cells inhibition by bioinformatics and in vitro studies

Hermawan

Ikawati

Jenie

et al. 2021

Saudi Pharmaceutical Journal

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show abstract

“…prostate, pancreatic, colon, breast, and gastric cancer (Song et al, 2016;Lim et al, 2017;Wang et al, 2019a) sensitizing chemotherapy CDKN2A, BCL2, CASP3/9, BAX, PTK2, MAPK14 lung and pancreatic cancer (Parashar et al, 2018;Lee et al, 2019) inhibiting metabolism AKT1, GTF2H2, MAP2K1/2, MAPK1, NFKB1, PIK3CA breast cancer (Harmon and Patel, 2004) enhancing immunity GZMB, ID2, IFNG, IRF2, SMAD3/7 lung cancer and melanoma (Lian et al, 2018) Naringin anti-proliferation AKT1, BIRC5, CDKN1A, CTNNB1, EGFR, MAPK1, MIR126, MTOR, NFKB, PIK3CA, VCAM1…”

Section: Discussionmentioning

confidence: 99%

Mapping Pharmacological Network of Multi-Targeting Litchi Ingredients in Cancer Therapeutics

Cao

Han

et al. 2020

Front. Pharmacol.

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Considerable pharmacological studies have demonstrated that the extracts and ingredients from different parts (seeds, peels, pulps, and flowers) of Litchi exhibited anticancer effects by affecting the proliferation, apoptosis, autophagy, metastasis, chemotherapy and radiotherapy sensitivity, stemness, metabolism, angiogenesis, and immunity via multiple targeting. However, there is no systematical analysis on the interaction network of "multiple ingredients-multiple targets-multiple pathways" anticancer effects of Litchi. In this study, we summarized the confirmed anticancer ingredients and molecular targets of Litchi based on published articles and applied network pharmacology approach to explore the complex mechanisms underlying these effects from a perspective of system biology. The top ingredients, top targets, and top pathways of each anticancer function were identified using network pharmacology approach. Further intersecting analyses showed that Epigallocatechin gallate (EGCG), Gallic acid, Kaempferol, Luteolin, and Betulinic acid were the top ingredients which might be the key ingredients exerting anticancer function of Litchi, while BAX, BCL2, CASP3, and AKT1 were the top targets which might be the main targets underling the anticancer mechanisms of these top ingredients. These results provided references for further understanding and exploration of Litchi as therapeutics in cancer as well as the application of "Component Formula" based on Litchi's effective ingredients.

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“…An alternative recent study demonstrated naringenin’s effectivity as an anticancer drug in breast cancer treatment is due to the activation of the caspase-3 protein and caspase-9 enzymes [ 107 ], while Kumar and co-workers showed in vivo that naringenin showed antitumor effects on skin cancer [ 108 ].…”

Section: Polyphenolsmentioning

confidence: 99%

Current Perspectives of the Applications of Polyphenols and Flavonoids in Cancer Therapy

et al. 2020

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The development of anticancer therapies that involve natural drugs has undergone exponential growth in recent years. Among the natural compounds that produce beneficial effects on human health, polyphenols have shown potential therapeutic applications in cancer due to their protective functions in plants, their use as food additives, and their excellent antioxidant properties. The possibility of combining conventional drugs—which are usually more aggressive than natural compounds—with polyphenols offers very valuable advantages such as the building of more efficient anticancer therapies with less side effects on human health. This review shows a wide range of trials in which polyphenolic compounds play a crucial role as anticancer medicines alone or in combination with other drugs at different stages of cancer: cancer initiation, promotion, and growth or progression. Moreover, the future directions in applications of various polyphenols in cancer therapy are emphasized.

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Naringenin has a chemoprotective effect in MDA‑MB‑231 breast cancer cells via inhibition of caspase‑3 and ‑9 activities

Cited by 27 publications

References 30 publications

Identification of potential therapeutic target of naringenin in breast cancer stem cells inhibition by bioinformatics and in vitro studies

Identification of potential therapeutic target of naringenin in breast cancer stem cells inhibition by bioinformatics and in vitro studies

Mapping Pharmacological Network of Multi-Targeting Litchi Ingredients in Cancer Therapeutics

Current Perspectives of the Applications of Polyphenols and Flavonoids in Cancer Therapy

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