Gold nanoparticles–conjugated quercetin induces apoptosis via inhibition of EGFR/PI3K/Akt–mediated pathway in breast cancer cell lines (MCF‐7 and MDA‐MB‐231)

Epidermal growth factor plays a major role in breast cancer cell proliferation, survival, and metastasis. Quercetin, a bioactive flavonoid, is shown to exhibit anticarcinogenic effects against various cancers including breast cancer. Hence, the present study was designed to evaluate the effects of g...

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Vydané v:Cell biochemistry and function Ročník 35; číslo 4; s. 217 - 231
Hlavní autori: Balakrishnan, Solaimuthu, Mukherjee, Sudip, Das, Sourav, Bhat, Firdous Ahmad, Raja Singh, Paulraj, Patra, Chitta Ranjan, Arunakaran, Jagadeesan
Médium: Journal Article
Jazyk:English
Vydavateľské údaje: England Wiley Subscription Services, Inc 01.06.2017
Predmet:
1-Phosphatidylinositol 3-kinase
AKT protein
Annexin V
Apoptosis
Apoptosis - drug effects
Assaying
BAX protein
Bcl-2 protein
Biocompatibility
Biomedical materials
Biotechnology
Breast cancer
Breast Neoplasms - drug therapy
Breast Neoplasms - metabolism
Breast Neoplasms - pathology
Cancer
Caspase
Caspase-3
Cell death
Cell growth
Cell proliferation
Cell survival
Condensation
Crystal structure
Cytotoxicity
Drug delivery
Drug delivery systems
Drug Delivery Systems - methods
EGFR
Epidermal growth factor
Epidermal growth factor receptors
Female
Glycogen Synthase Kinase 3 beta - metabolism
Gold
Gold - chemistry
gold nanoparticles and quercetin
Humans
Immunoblotting
Immunocytochemistry
MAP Kinase Signaling System - drug effects
MCF-7 Cells
Metal Nanoparticles
Metastases
Nanoparticles
Phosphatidylinositol 3-Kinases - metabolism
Proteins
Proto-Oncogene Proteins c-akt - metabolism
Quercetin - chemistry
Quercetin - pharmacology
Signal transduction
Signaling
Staining
Surgical implants
Survival
Therapy
TOR Serine-Threonine Kinases - metabolism
Tumor cell lines
gold nanoparticles and quercetin
apoptosis
breast cancer
drug delivery
EGFR
ISSN:0263-6484, 1099-0844, 1099-0844
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Shrnutí:Epidermal growth factor plays a major role in breast cancer cell proliferation, survival, and metastasis. Quercetin, a bioactive flavonoid, is shown to exhibit anticarcinogenic effects against various cancers including breast cancer. Hence, the present study was designed to evaluate the effects of gold nanoparticles–conjugated quercetin (AuNPs‐Qu‐5) in MCF‐7 and MDA‐MB‐231 breast cancer cell lines. Borohydride reduced AuNPs were synthesized and conjugated with quercetin to yield AuNPs‐Qu‐5. Both were thoroughly characterized by several physicochemical techniques, and their cytotoxic effects were assessed by MTT assay. Apoptotic studies such as DAPI, AO/EtBr dual staining, and annexin V‐FITC staining were performed. AuNPs and AuNPs‐Qu‐5 were spherical with crystalline nature, and the size of particles range from 3.0 to 4.5 nm. AuNPs‐Qu‐5 exhibited lower IC50 value compared to free Qu. There was a considerable increase in apoptotic population with increased nuclear condensation seen upon treatment with AuNPs‐Qu‐5. To delineate the molecular mechanism behind its apoptotic role, we analysed the proteins involved in apoptosis and epidermal growth factor receptor (EGFR)–mediated PI3K/Akt/GSK‐3β signalling by immunoblotting and immunocytochemistry. The pro‐apoptotic proteins (Bax, Caspase‐3) were found to be up regulated and anti‐apoptotic protein (Bcl‐2) was down regulated on treatment with AuNPs‐Qu‐5. Additionally, AuNPs‐Qu‐5 treatment inhibited the EGFR and its downstream signalling molecules PI3K/Akt/mTOR/GSK‐3β. In conclusion, administration of AuNPs‐Qu‐5 in breast cancer cell lines curtails cell proliferation through induction of apoptosis and also suppresses EGFR signalling. AuNPs‐Qu‐5 is more potent than free quercetin in causing cancer cell death, and hence, this could be a potential drug delivery system in breast cancer therapy.
Bibliografia:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
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ISSN:0263-6484
1099-0844
1099-0844
DOI:10.1002/cbf.3266