Deciphering the binding behavior of flavonoids to the cyclin dependent kinase 6/cyclin D complex

Zhang, Jingxiao; Zhang, Lilei; Xu, Yangcheng; Jiang, Shanshan; Shao, Yueyue

doi:10.1371/journal.pone.0196651

Cited by 21 publications

(13 citation statements)

References 46 publications

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“…These results suggest that the A. hierochuntica treatment may suppress the cell cycle progression, by down-regulating the expression of Cyclin D1 and E and induce apoptosis through p53 and p21. This could be due to the rich source of phenols and flavonoids, widely reported to be cyclin inhibitors ( Mocanu et al, 2015 , Zhang et al, 2018 ), and recently identified in the methanolic leaf extracts of A. hierochuntica ( Saranya et al, 2019 ).…”

Section: Discussionmentioning

confidence: 99%

Anastatica hierochuntica (L.) methanolic and aqueous extracts exert antiproliferative effects through the induction of apoptosis in MCF-7 breast cancer cells

Rameshbabu¹,

Messaoudi

Alehaideb

et al. 2020

Saudi Pharmaceutical Journal

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Breast cancer therapy using anticancer bioactive compounds derived from natural products as adjuvant treatment has gained recognition due to expensive and toxic conventional chemotherapeutic drugs. The whole plant of Anastatica hierochuntica (L.) ( A. hierochuntica ) has been investigated for its pharmacologically important anticancer properties but without categorizing the biological activities of the plant parts. We assessed the anticancer potential of different parts of A. hierochuntica (seeds, stems and leaves) and explored their mechanisms of action using the human breast cancer cell line, MCF-7. Currently, we investigated the antiproliferative effects of methanolic (MSD, MST, ML) and aqueous (ASD, AST, AL) extracts of A. hierochuntica plant parts on the MCF-7 cells using cell viability assays. Flow cytometry, Western Blot, DNA fragmentation, and gene expression assays were performed to evaluate apoptosis and cell cycle regulatory proteins. The results indicate that the methanolic and aqueous extracts decreased MCF-7 cell viability in a dose-dependent manner. The induction of apoptosis was observed in all the methanolic and aqueous-treated MCF-7 cells. The cell death process was confirmed by the visualization of DNA fragmentation and cleavage of the intrinsic apoptotic pathways, caspase-9 and caspase-3, the key enzyme causing apoptosis hallmarks. In addition, the most pro-apoptotic extracts, ASD and ML, up-regulated the expression of pro-apoptotic Bax, tumor suppressor TP53 genes and the cyclin inhibitor CDKN1A gene. In conclusion, of the aqueous and methanolic extracts of A. hierochuntica plant parts exerting antiproliferative effects through the induction of apoptosis in breast cancer MCF-7 cells, ASD and ML extracts were the most promising natural-based drugs for the treatment of breast cancer.

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Section: Discussionmentioning

confidence: 99%

Anastatica hierochuntica (L.) methanolic and aqueous extracts exert antiproliferative effects through the induction of apoptosis in MCF-7 breast cancer cells

Rameshbabu¹,

Messaoudi

Alehaideb

et al. 2020

Saudi Pharmaceutical Journal

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“…This approach based on the molecular mechanics Poisson–Boltzmann surface area (MM/PBSA) and is a common method for calculating the binding free energy between target and ligand. The calculation of the free energy always follows the same formula [ 81 ] and the corresponding equations have already been presented in numerous publications [ 82 , 83 , 84 ]. The temperature was adjusted to 298.15 K according to the MD simulation parameters.…”

Section: Methodsmentioning

confidence: 99%

Detailed Analysis of 17β-Estradiol-Aptamer Interactions: A Molecular Dynamics Simulation Study

Eisold

Labudde

2018

Molecules

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Micro-pollutants such as 17β-Estradiol (E2) have been detected in different water resources and their negative effects on the environment and organisms have been observed. Aptamers are established as a possible detection tool, but the underlying ligand binding is largely unexplored. In this study, a previously described 35-mer E2-specific aptamer was used to analyse the binding characteristics between E2 and the aptamer with a MD simulation in an aqueous medium. Because there is no 3D structure information available for this aptamer, it was modeled using coarse-grained modeling method. The E2 ligand was positioned inside a potential binding area of the predicted aptamer structure, the complex was used for an 25 ns MD simulation, and the interactions were examined for each time step. We identified E2-specific bases within the interior loop of the aptamer and also demonstrated the influence of frequently underestimated water-mediated hydrogen bonds. The study contributes to the understanding of the behavior of ligands binding with aptamer structure in an aqueous solution. The developed workflow allows generating and examining further appealing ligand-aptamer complexes.

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“…The hydrogen-bonding force and van der Waals interactions with residues Ile19, Val27, Ala41, Glu61, Phe98, Gln103, Aap163, and Leu152 contributed to the binding affinity. These binding features of flavonoid inhibitors may provide valuable insight into the development of CDK6 inhibitors as chemopreventive agents [ 39 ].…”

Section: Cmda Of Catechin-protein Interactionmentioning

confidence: 99%

Computational Molecular Docking and X-ray Crystallographic Studies of Catechins in New Drug Design Strategies

et al. 2018

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Epidemiological and laboratory studies have shown that green tea and green tea catechins exert beneficial effects on a variety of diseases, including cancer, metabolic syndrome, infectious diseases, and neurodegenerative diseases. In most cases, (−)-epigallocatechin gallate (EGCG) has been shown to play a central role in these effects by green tea. Catechins from other plant sources have also shown health benefits. Many studies have revealed that the binding of EGCG and other catechins to proteins is involved in its action mechanism. Computational docking analysis (CMDA) and X-ray crystallographic analysis (XCA) have provided detailed information on catechin-protein interactions. Several of these studies have revealed that the galloyl moiety anchors it to the cleft of proteins through interactions with its hydroxyl groups, explaining the higher activity of galloylated catechins such as EGCG and epicatechin gallate than non-galloylated catechins. In this paper, we review the results of CMDA and XCA of EGCG and other plant catechins to understand catechin-protein interactions with the expectation of developing new drugs with health-promoting properties.

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Deciphering the binding behavior of flavonoids to the cyclin dependent kinase 6/cyclin D complex

Cited by 21 publications

References 46 publications

Anastatica hierochuntica (L.) methanolic and aqueous extracts exert antiproliferative effects through the induction of apoptosis in MCF-7 breast cancer cells

Anastatica hierochuntica (L.) methanolic and aqueous extracts exert antiproliferative effects through the induction of apoptosis in MCF-7 breast cancer cells

Detailed Analysis of 17β-Estradiol-Aptamer Interactions: A Molecular Dynamics Simulation Study

Computational Molecular Docking and X-ray Crystallographic Studies of Catechins in New Drug Design Strategies

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