Modulatory Effects of Biosynthesized Gold Nanoparticles Conjugated with Curcumin and Paclitaxel on Tumorigenesis and Metastatic Pathways-In Vitro and In Vivo Studies.
Animals
Antineoplastic Agents
/ pharmacology
Apoptosis
/ drug effects
Carcinogenesis
/ drug effects
Cell Line
Cell Line, Tumor
Curcumin
/ pharmacology
Drug Resistance, Multiple
/ drug effects
Female
Gold
/ pharmacology
HEK293 Cells
Humans
Metal Nanoparticles
/ administration & dosage
Mice
Mice, Inbred BALB C
Neoplasm Metastasis
/ drug therapy
Paclitaxel
/ pharmacology
Triple Negative Breast Neoplasms
/ drug therapy
Curcumin
Paclitaxel
gold nanoparticles
metastasis
triple-negative breast cancer cell lines (4T1 and MDA MB 231)
Journal
International journal of molecular sciences
ISSN: 1422-0067
Titre abrégé: Int J Mol Sci
Pays: Switzerland
ID NLM: 101092791
Informations de publication
Date de publication:
15 Feb 2022
15 Feb 2022
Historique:
received:
11
12
2021
revised:
05
02
2022
accepted:
07
02
2022
entrez:
26
2
2022
pubmed:
27
2
2022
medline:
19
3
2022
Statut:
epublish
Résumé
Breast cancer is the most common cancer in women globally, and diagnosing it early and finding potential drug candidates against multi-drug resistant metastatic breast cancers provide the possibilities of better treatment and extending life. The current study aimed to evaluate the synergistic anti-metastatic activity of Curcumin (Cur) and Paclitaxel (Pacli) individually, the combination of Curcumin-Paclitaxel (CP), and also in conjugation with gold nanoparticles (AuNP-Curcumin (Au-C), AuNP-Paclitaxel (Au-P), and AuNP-Curcumin-Paclitaxel (Au-CP)) in various in vitro and in vivo models. The results from combination treatments of CP and Au-CP demonstrated excellent synergistic cytotoxic effects in triple-negative breast cancer cell lines (MDA MB 231 and 4T1) in in vitro and in vivo mouse models. Detailed mechanistic studies were performed that reveal that the anti-cancer effects were associated with the downregulation of the expression of VEGF, CYCLIN-D1, and STAT-3 genes and upregulation of the apoptotic Caspase-9 gene. The group of mice that received CP combination therapy (with and without gold nanoparticles) showed a significant reduction in the size of tumor when compared to the Pacli alone treatment and control groups. Together, the results suggest that the delivery of gold conjugated Au-CP formulations may help in modulating the outcomes of chemotherapy. The present study is well supported with observations from cell-based assays, molecular and histopathological analyses.
Sections du résumé
BACKGROUND
BACKGROUND
Breast cancer is the most common cancer in women globally, and diagnosing it early and finding potential drug candidates against multi-drug resistant metastatic breast cancers provide the possibilities of better treatment and extending life.
METHODS
METHODS
The current study aimed to evaluate the synergistic anti-metastatic activity of Curcumin (Cur) and Paclitaxel (Pacli) individually, the combination of Curcumin-Paclitaxel (CP), and also in conjugation with gold nanoparticles (AuNP-Curcumin (Au-C), AuNP-Paclitaxel (Au-P), and AuNP-Curcumin-Paclitaxel (Au-CP)) in various in vitro and in vivo models.
RESULTS
RESULTS
The results from combination treatments of CP and Au-CP demonstrated excellent synergistic cytotoxic effects in triple-negative breast cancer cell lines (MDA MB 231 and 4T1) in in vitro and in vivo mouse models. Detailed mechanistic studies were performed that reveal that the anti-cancer effects were associated with the downregulation of the expression of VEGF, CYCLIN-D1, and STAT-3 genes and upregulation of the apoptotic Caspase-9 gene. The group of mice that received CP combination therapy (with and without gold nanoparticles) showed a significant reduction in the size of tumor when compared to the Pacli alone treatment and control groups.
CONCLUSIONS
CONCLUSIONS
Together, the results suggest that the delivery of gold conjugated Au-CP formulations may help in modulating the outcomes of chemotherapy. The present study is well supported with observations from cell-based assays, molecular and histopathological analyses.
Identifiants
pubmed: 35216264
pii: ijms23042150
doi: 10.3390/ijms23042150
pmc: PMC8876049
pii:
doi:
Substances chimiques
Antineoplastic Agents
0
Gold
7440-57-5
Curcumin
IT942ZTH98
Paclitaxel
P88XT4IS4D
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
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