Decrypting the Molecular Mechanistic Pathways Delineating the Chemotherapeutic Potential of Ruthenium-Phloretin Complex in Colon Carcinoma Correlated with the Oxidative Status and Increased Apoptotic Events.
Aberrant Crypt Foci
/ pathology
Animals
Antioxidants
/ pharmacology
Apoptosis
/ drug effects
Benzothiazoles
/ chemistry
Biphenyl Compounds
/ chemistry
Cell Proliferation
/ drug effects
Cell Survival
/ drug effects
Colon
/ drug effects
Colonic Neoplasms
/ blood
DNA
/ metabolism
Female
Free Radical Scavengers
/ pharmacology
HT29 Cells
Humans
Kidney
/ drug effects
Male
Matrix Metalloproteinase 9
/ metabolism
Mice, Inbred BALB C
NF-kappa B
/ metabolism
Oxidation-Reduction
Phloretin
/ chemistry
Picrates
/ chemistry
Ruthenium
/ chemistry
Spectroscopy, Fourier Transform Infrared
Sulfonic Acids
/ chemistry
Toxicity Tests
bcl-2-Associated X Protein
/ metabolism
Journal
Oxidative medicine and cellular longevity
ISSN: 1942-0994
Titre abrégé: Oxid Med Cell Longev
Pays: United States
ID NLM: 101479826
Informations de publication
Date de publication:
2020
2020
Historique:
received:
21
01
2020
revised:
17
03
2020
accepted:
06
04
2020
entrez:
23
6
2020
pubmed:
23
6
2020
medline:
28
1
2021
Statut:
epublish
Résumé
To explore fresh strategies in colorectal cancer (CRC) chemotherapy, we evaluated the capability of the ruthenium-phloretin complex in exterminating colon cancer by effectively addressing multiple apoptotic mechanisms on HT-29 cancer cells together with an animal model of colorectal cancer activated by 1,2-dimethylhydrazine and dextran sulfate sodium. Our current approach offers tangible evidence of the application of the ruthenium-phloretin complex in future chemotherapy. The complex triggers intrinsic apoptosis triggered by p53 and modulates the Akt/mTOR pathway along with other inflammatory biomarkers. The ruthenium-phloretin complex has been synthesized and successfully characterized by numerous spectroscopic methodologies accompanied by DPPH, FRAP, and ABTS assays assessing its antioxidant potential. Studies conducted in human cell lines revealed that the complex improved levels of p53 and caspase-3 while diminishing the activities of VEGF and mTOR, triggers apoptosis, and induces fragmentation of DNA in the HT-29 cells. Toxicity studies were conducted to identify the therapeutic doses of the novel complex in animal models. The outcomes of the in vivo report suggest that the complex was beneficial in repressing multiplicity of aberrant crypt foci as well as hyperplastic lesions and also promoted increased levels of CAT, SOD, and glutathione. In addition, the ruthenium-phloretin complex was able to control cell proliferation and boosted apoptotic outbursts in cancer cells associated with the increase in cellular response towards Bax while diminishing responses towards Bcl-2, NF-
Identifiants
pubmed: 32566099
doi: 10.1155/2020/7690845
pmc: PMC7281810
doi:
Substances chimiques
Antioxidants
0
Benzothiazoles
0
Biphenyl Compounds
0
Free Radical Scavengers
0
NF-kappa B
0
Picrates
0
Sulfonic Acids
0
bcl-2-Associated X Protein
0
2,2'-azino-di-(3-ethylbenzothiazoline)-6-sulfonic acid
28752-68-3
Ruthenium
7UI0TKC3U5
DNA
9007-49-2
calf thymus DNA
91080-16-9
1,1-diphenyl-2-picrylhydrazyl
DFD3H4VGDH
Matrix Metalloproteinase 9
EC 3.4.24.35
Phloretin
S5J5OE47MK
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
7690845Informations de copyright
Copyright © 2020 Guoguo Jin et al.
Déclaration de conflit d'intérêts
The authors have declared that no competing interest exists.
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