PMID- 37732363
OWN - NLM
STAT- Publisher
LR  - 20231127
IS  - 1538-0254 (Electronic)
IS  - 0739-1102 (Linking)
DP  - 2023 Sep 21
TI  - Exploring the molecular interactions and binding affinity of resveratrol and 
      calcitriol with RAGE and its intracellular proteins and kinases involved in 
      colorectal cancer.
PG  - 1-24
LID - 10.1080/07391102.2023.2258993 [doi]
AB  - Colorectal cancer (CRC) burden is progressively increasing in young population 
      due to dietary and lifestyle pattern. Advanced glycation end products (AGEs), one 
      of the dietary compounds, form complex aggregates with proteins, lipids, and 
      nucleic acids distorting their structure and function. AGE's pro-tumorigenic role 
      is mediated through the receptor for AGEs (RAGE) triggering an array of signaling 
      pathways. The current study aimed to target AGE-RAGE axis signaling proteins and 
      kinases at multiple levels with calcitriol (CAL) and trans-resveratrol (RES) 
      through in silico analysis using molecular docking (MD), molecular dynamic 
      simulation(MDS), MM-PBSA analysis, and in vitro study. In silico analysis of CAL 
      and RES showed significant binding affinity toward RAGE and its signaling 
      proteins such as NF-kB, PI3K/AKT, ERK1/2, and PKC compared to its reference 
      inhibitors through better hydrogen, hydrophobic, pi-pi stacking interactions. MD 
      and MDS studies have revealed stable and compact protein-ligand complexes. 
      Binding free energies of protein-ligand complex were estimated using MM/PBSA 
      analysis thatprovided an assessment of overall interacting free energies of 
      complexes and revealed the presence of low binding energy within the active site. 
      Furthermore, in the in vitro study, methylglyoxal (MG), an AGE-precursor showed a 
      proliferative effect on HCT116, however, CAL and RES showed an inhibitory effect 
      against MG induced effect with an IC50 value of 51 nM and 110 microM respectively. 
      Thus, the study suggests the possible target binding sites of AGE-RAGE signaling 
      proteins and kinases with CAL and RES, thereby exploiting it for developing CAL 
      with RES as adjuvant therapy along with chemo drug for CRC.Communicated by 
      Ramaswamy H. Sarma.
FAU - Muthyalaiah, Yadav Sangeeta
AU  - Muthyalaiah YS
AD  - Department of Biomedical Sciences, Sri Ramachandra Institute of Higher Education 
      and Research, Chennai, India.
FAU - Arockiasamy, Sumathy
AU  - Arockiasamy S
AD  - Department of Biomedical Sciences, Sri Ramachandra Institute of Higher Education 
      and Research, Chennai, India.
FAU - P A, Abhinand
AU  - P A A
AD  - Department of Bioinformatics, Sri Ramachandra Institute of Higher Education and 
      Research, Chennai, India.
LA  - eng
PT  - Journal Article
DEP - 20230921
PL  - England
TA  - J Biomol Struct Dyn
JT  - Journal of biomolecular structure & dynamics
JID - 8404176
SB  - IM
OTO - NOTNLM
OT  - AGE-RAGE axis
OT  - AGEs
OT  - RAGE
OT  - calcitriol
OT  - colorectal cancer
OT  - intracellular signaling
OT  - molecular docking
OT  - protein kinases
OT  - trans-resveratrol
EDAT- 2023/09/21 06:42
MHDA- 2023/09/21 06:42
CRDT- 2023/09/21 04:18
PHST- 2023/09/21 06:42 [pubmed]
PHST- 2023/09/21 06:42 [medline]
PHST- 2023/09/21 04:18 [entrez]
AID - 10.1080/07391102.2023.2258993 [doi]
PST - aheadofprint
SO  - J Biomol Struct Dyn. 2023 Sep 21:1-24. doi: 10.1080/07391102.2023.2258993.