Cytotoxic Activities of Amentoflavone against Human Breast and Cervical Cancers are Mediated by Increasing of PTEN Expression Levels due to Peroxisome Proliferator-Activated Receptor γ Activation

Lee, Eunjung; Shin, Soyoung; Lee, Jee Young; Lee, So-Jung; Kim, Jin-Kyoung; Yoon, Do‐Young; Woo, Eun‐Rhan; Kim, Yangmee

doi:10.5012/bkcs.2012.33.7.2219

Cited by 15 publications

(8 citation statements)

References 27 publications

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“…Biflavonoids, on the other hand, do not present this feature; however, they were reported as potentially mutagenic [ 76 ]. Nonetheless, such negative effects are only present at concentrations between 100 and 250 μM [ 77 , 78 ]. As such, based on the IC 50 values of both quercetin and amentoflavone, flavonoids have significant potential as epi-nutraceutics.…”

Section: Discussionmentioning

confidence: 99%

Flavonoids as Putative Epi-Modulators: Insight into Their Binding Mode with BRD4 Bromodomains Using Molecular Docking and Dynamics

Prieto‐Martínez

Medina-Franco

2018

Biomolecules

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Flavonoids are widely recognized as natural polydrugs, given their anti-inflammatory, antioxidant, sedative, and antineoplastic activities. Recently, different studies showed that flavonoids have the potential to inhibit bromodomain and extraterminal (BET) bromodomains. Previous reports suggested that flavonoids bind between the Z and A loops of the bromodomain (ZA channel) due to their orientation and interactions with P86, V87, L92, L94, and N140. Herein, a comprehensive characterization of the binding modes of fisetin and the biflavonoid, amentoflavone, is discussed. To this end, both compounds were docked with BET bromodomain 4 (BRD4) using four docking programs. The results were post-processed with protein–ligand interaction fingerprints. To gain further insight into the binding mode of the two natural products, the docking results were further analyzed with molecular dynamics simulations. The results showed that amentoflavone makes numerous contacts in the ZA channel, as previously described for flavonoids and kinase inhibitors. It was also found that amentoflavone can potentially make contacts with non-canonical residues for BET inhibition. Most of these contacts were not observed with fisetin. Based on these results, amentoflavone was experimentally tested for BRD4 inhibition, showing activity in the micromolar range. This work may serve as the basis for scaffold optimization and the further characterization of flavonoids as BET inhibitors.

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Section: Discussionmentioning

confidence: 99%

Flavonoids as Putative Epi-Modulators: Insight into Their Binding Mode with BRD4 Bromodomains Using Molecular Docking and Dynamics

Prieto‐Martínez

Medina-Franco

2018

Biomolecules

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“…This impressive effect of 1,2,3,4,6-tetra- O -galloyl- β -D-glucose could be achieved through targeting on the overexpression of lactic acid dehydrogenase-A and metabolism genes of MDA-MB-231 cancer cells [ 34 , 58 ]. The molecular mechanisms underlying the activities of amentoflavone mainly involve the action on human peroxisome proliferator-activated receptor gamma and mitochondria-emanated intrinsic pathways [ 73 , 74 ]. Moreover, amentoflavone also could suppress the expression of NF-кB and VEGF and thus obstruct the tumour angiogenesis and metastasis [ 44 , 75 ].…”

Section: Pharmacological Insights Of Anticancer Aspectmentioning

confidence: 99%

Gallnuts: A Potential Treasure in Anticancer Drug Discovery

Gao

Yang

Yin

et al. 2018

Evidence-Based Complementary and Alternative Medicine

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Introduction. In the discovery of more potent and selective anticancer drugs, the research continually expands and explores new bioactive metabolites coming from different natural sources. Gallnuts are a group of very special natural products formed through parasitic interaction between plants and insects. Though it has been traditionally used as a source of drugs for the treatment of cancerous diseases in traditional and folk medicinal systems through centuries, the anticancer properties of gallnuts are barely systematically reviewed. Objective. To evidence the traditional uses and phytochemicals and pharmacological mechanisms in anticancer aspects of gallnuts, a literature review was performed. Materials and Methods. The systematic review approach consisted of searching web-based scientific databases including PubMed, Web of Science, and Science Direct. The keywords for searching include gallnut, Galla Chinensis, Rhus chinensis, Rhus potaninii, Rhus punjabensis, nutgall, gall oak, Quercus infectoria, Quercus lusitanica, and galla turcica. Two reviewers extracted papers independently to remove the papers unrelated to the anticancer properties of gallnuts. Patents, abstracts, case reports, and abstracts in symposium and congress were excluded. Results and Conclusion. As a result, 14 articles were eligible to be evaluated. It is primarily evident that gallnuts contain a number of bioactive metabolites, which account for anticancer activities. The phytochemical and pharmacological studies reviewed strongly underpin a fundamental understanding of anticancer properties for gallnuts (Galla Chinensis and Galla Turcica) and support their ongoing clinical uses in China. The further bioactive compounds screening and evaluation, pharmacological investigation, and clinical trials are expected to progress gallnut-based development to finally transform the wild medicinal gallnuts to the valuable authorized anticancer drugs.

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“…Compound 2 was previously reported as a weak cytotoxic agent against lung cancer cells A549. However, it was shown to possess potent cytotoxic effects against both MCF‐7 and HeLa cells, with the IC 50 values of 25 and 20 μM, respectively (Lee et al, ).…”

Section: Resultsmentioning

confidence: 99%

Growth inhibitory activity of biflavonoids and diterpenoids from the leaves of the Libyan Juniperus phoenicea against human cancer cells

Groshi

Jasim

Evans

et al. 2019

Phytotherapy Research

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Three biflavonoids [cupressuflavone (1), amentoflavone (2), and sumaflavone (3)], four diterpenoids [13-epi-cupressic acid (4), imbricatholic acid (5), 3-hydroxysandaracopimaric acid (6), and dehydroabietic acid (7)], and one lignan [β-peltatin methyl ether (8)] were isolated from the cytotoxic fractions of the extracts of the leaves of the Libyan Juniperus phoenicea L. The structures of these compounds were elucidated by spectroscopic means. Cytotoxicity of compounds 1-6 were assessed against the human lung cancer cell line A549 using the MTT assay. Compounds 1 and 3 showed cytotoxicity against the A549 cells (IC 50 = 65 and 77 μM, respectively), whereas compound 2 did not show any activity. Diterpenes 4-6 exhibited weak cytotoxicity against the A549 cells with the IC 50 values of 159, 263, and 223 μM, respectively. The cytotoxicity of each compound was compared with the anticancer drug, etoposide (IC 50 = 61 μM). Cupressuflavone (1) was evaluated also for cytotoxicity against both the human PC3 cancer cell line and the normal prostate cell line (PNT2), and this compound revealed a high degree of cytotoxic selectivity towards the prostate cancer cells (PC3), with IC 50 value of 19.9 μM, without any evidence of cytotoxicity towards the normal prostate cell line (PNT2).

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Cytotoxic Activities of Amentoflavone against Human Breast and Cervical Cancers are Mediated by Increasing of PTEN Expression Levels due to Peroxisome Proliferator-Activated Receptor γ Activation

Cited by 15 publications

References 27 publications

Flavonoids as Putative Epi-Modulators: Insight into Their Binding Mode with BRD4 Bromodomains Using Molecular Docking and Dynamics

Flavonoids as Putative Epi-Modulators: Insight into Their Binding Mode with BRD4 Bromodomains Using Molecular Docking and Dynamics

Gallnuts: A Potential Treasure in Anticancer Drug Discovery

Growth inhibitory activity of biflavonoids and diterpenoids from the leaves of the Libyan Juniperus phoenicea against human cancer cells

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