Deciphering the multi-scale mechanism of herbal phytoconstituents in targeting breast cancer: a computational pharmacological perspective.
Breast Neoplasms
/ drug therapy
Humans
Female
Molecular Docking Simulation
Estrogen Receptor alpha
/ metabolism
Sitosterols
/ pharmacology
Resveratrol
/ pharmacology
Alkaloids
/ pharmacology
Antineoplastic Agents, Phytogenic
/ pharmacology
Quercetin
/ pharmacology
Gallic Acid
/ pharmacology
Phytochemicals
/ pharmacology
Stilbenes
/ pharmacology
Network Pharmacology
Aromatase
Piperidines
Benzodioxoles
Polyunsaturated Alkamides
Breast cancer
Herbal phytoconstituents
Molecular docking
Molecular dynamics
Network pharmacology
Ayurveda
Traditional Medicine
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
11 Oct 2024
11 Oct 2024
Historique:
received:
29
06
2024
accepted:
01
10
2024
medline:
12
10
2024
pubmed:
12
10
2024
entrez:
11
10
2024
Statut:
epublish
Résumé
Breast Cancer (BC) is the most common cause of cancer-associated deaths in females worldwide. Despite advancements in BC treatment driven by extensive characterization of its molecular hallmarks, challenges such as drug resistance, tumor relapse, and metastasis persist. Therefore, there is an urgent need for alternative treatment approaches with multi-modal efficacy to overcome these hurdles. In this context, natural bioactives are increasingly recognized for their pivotal role as anti-cancer compounds. This study focuses on predicting molecular targets for key herbal phytoconstituents-gallic acid, piperine, quercetin, resveratrol, and beta-sitosterol-present in the polyherbal formulation, Krishnadi Churna. Using an in-silico network pharmacology model, key genes were identified and docked against these marker compounds and controls. Mammary carcinoma emerged as the most significant phenotype of the putative targets. Analysis of an online database revealed that out of 135 predicted targets, 134 were mutated in breast cancer patients. Notably, ESR1, CYP19A1, and EGFR were identified as key genes which are known to regulate the BC progression. Docking studies demonstrated that the herbal phytoconstituents had similar or better docking scores than positive controls for these key genes, with convincing protein-ligand interactions confirmed by molecular dynamics simulations, MM/GBSA and free energy landscape (FEL) analysis. Overall, this study highlights the predictive potential of herbal phytoconstituents in targeting BC genes, suggesting their promise as a basis for developing new therapeutic formulations for BC.
Identifiants
pubmed: 39394443
doi: 10.1038/s41598-024-75059-z
pii: 10.1038/s41598-024-75059-z
doi:
Substances chimiques
Estrogen Receptor alpha
0
Sitosterols
0
gamma-sitosterol
5LI01C78DD
ESR1 protein, human
0
Resveratrol
Q369O8926L
Alkaloids
0
Antineoplastic Agents, Phytogenic
0
CYP19A1 protein, human
EC 1.14.14.1
piperine
U71XL721QK
Quercetin
9IKM0I5T1E
Gallic Acid
632XD903SP
Phytochemicals
0
Stilbenes
0
Aromatase
EC 1.14.14.1
Piperidines
0
Benzodioxoles
0
Polyunsaturated Alkamides
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
23795Informations de copyright
© 2024. The Author(s).
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