Dataset Information

Molecular docking analysis of nuclear factor-?B and genistein interaction in the context of breast cancer.

ABSTRACT: Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-?B) is a transcription factor and it contributes to breast cancer growth and metastasis. Hence, NF-?B is considered as a target for anti-breast cancer drugs. NF-?B was retrieved from the UniProtKB Data Base with UniProt ID P19838, its energy was minimized and subjected to molecular dynamic simulations using Gromacs v5.0.7 software with GROMOS96 43A1 force field implementing the steepest descent algorithm. The structure of genistein was retrieved from NCBI PubChem database in .sdf format and convert to .pdb format. The genistein compound was docked into the active site of NF-?B proteins with AutoDock tools 1.5. The genistein compound displayed the best binding energies at -6.29 (NF-?B) kcal/mol correspondingly. The binding interactions of this compound with the active site of NF-?B proteins suggested that amino acid residues (Lys52, Ser243, Asp274, Lys, 275) might play a key role in anti-breast cancer activity. Genistein also inhibited the translocation and expression of NF-?B in the nucleus of both breast cancer cell lines. These findings might increase our understanding of the molecular and functional role of NF-?B in breast cancer. It could also help in developing additional druggable NF-?B inhibitors with high potency, specificity and outstanding bioavailability.

SUBMITTER: Mukund V

PROVIDER: S-EPMC6651031 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Molecular docking analysis of nuclear factor-κB and genistein interaction in the context of breast cancer.

Mukund Vidya V Behera Santosh Kumar SK Alam Afroz A Nagaraju Ganji Purnachandra GP

Bioinformation 20190131 1

Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) is a transcription factor and it contributes to breast cancer growth and metastasis. Hence, NF-κB is considered as a target for anti-breast cancer drugs. NF-κB was retrieved from the UniProtKB Data Base with UniProt ID P19838, its energy was minimized and subjected to molecular dynamic simulations using Gromacs v5.0.7 software with GROMOS96 43A1 force field implementing the steepest descent algorithm. The structure of geniste ...[more]

PMID: 31359993

Similar Datasets

Project description:Transgelin 2 (TAGLN2) is a cytoskeletal protein of the calponin family. Abnormal expression of TAGLN2 was observed in various types of cancer. Our previous study reported that TAGLN2 expression was reduced in lymph node‑positive breast cancer patients; however, the role of TAGLN2 in breast cancer metastasis remains unknown. In the present study, the role of TAGLN2 in breast cancer metastasis was investigated in vitro and in vivo via Transwell migration, luciferase and flow cytometry assays, and a mouse xenograft model. Proteins interacting with TAGLN2 were identified via co‑immunoprecipitation assays and liquid chromatography/mass spectrometry, and the signaling pathway associated with the effects of TAGLN2 was investigated. Additionally, western blotting and reverse transcription‑quantitative polymerase chain reaction were performed to further explore the potential pathway in which TAGLN2 may be involved and the mechanism underlying its effects in breast cancer metastasis. The present study reported that TAGLN2 expression was increased by 11.4‑fold in patients without distant metastasis compared with those positive for distant metastasis. Knockdown of TAGLN2 resulted in increased cell migration in vitro and promoted lung metastasis in vivo. Additionally, overexpression of TAGLN2 suppressed lung metastasis in a mouse model. Peroxiredoxin 1 (PRDX1), an important reactive oxygen species (ROS) regulator, was revealed to interact with TAGLN2. In addition, mitochondrial redistribution and PRDX1 downregulation were reported following TAGLN2 silencing, which promoted ROS production and nuclear factor (NF)‑κB activation in breast cancer cells. This induced the expression of metastasis‑associated genes, including C‑X‑C chemokine receptor 4, matrix metalloproteinase (MMP)1 and MMP2. The present study proposed TAGLN2 to function as a tumor suppressor and that loss of TAGLN2 may promote the metastasis of breast cancer by activating the ROS/NF‑κB signaling pathway.

Project description:Current prognostic factors are insufficient for precise risk-discrimination in breast cancer patients with low grade breast tumors, which, in disagreement with theoretical prognosis, occasionally form early lymph node metastasis. To identify markers for this group of patients, we employed iTRAQ-2DLC-MS/MS proteomics to 24 lymph node positive and 24 lymph node negative grade 1 luminal A primary breast tumors. Another group of 48 high-grade tumors (luminal B, triple negative, Her-2 subtypes) was also analyzed to investigate marker specificity for grade 1 luminal A tumors. From the total of 4405 proteins identified (FDR < 5%), the top 65 differentially expressed together with 30 previously identified and control markers were analyzed also at transcript level. Increased levels of carboxypeptidase B1 (CPB1), PDZ and LIM domain protein 2 (PDLIM2), and ring finger protein 25 (RNF25) were associated specifically with lymph node positive grade 1 tumors, whereas stathmin 1 (STMN1) and thymosin beta 10 (TMSB10) associated with aggressive tumor phenotype also in high grade tumors at both protein and transcript level. For CPB1, these differences were also observed by immunohistochemical analysis on tissue microarrays. Up-regulation of putative biomarkers in lymph node positive (versus negative) luminal A tumors was validated by gene expression analysis of an independent published data set (n = 343) for CPB1 (p = 0.00155), PDLIM2 (p = 0.02027) and RELA (p = 0.00015). Moreover, statistically significant connections with patient survival were identified in another public data set (n = 1678). Our findings indicate unique pro-metastatic mechanisms in grade 1 tumors that can include up-regulation of CPB1, activation of NF-κB pathway and changes in cell survival and cytoskeleton. These putative biomarkers have potential to identify the specific minor subpopulation of breast cancer patients with low grade tumors who are at higher than expected risk of recurrence and who would benefit from more intensive follow-up and may require more personalized therapy.

Dataset Information

Molecular docking analysis of nuclear factor-?B and genistein interaction in the context of breast cancer.

Publications

Molecular docking analysis of nuclear factor-κB and genistein interaction in the context of breast cancer.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets