Exploring Amodiaquine's Repurposing Potential in Breast Cancer Treatment-Assessment of In-Vitro Efficacy & Mechanism of Action.
3D spheroids
amodiaquine
apoptosis
autophagy
breast cancer
drug repurposing
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:
28 Sep 2022
28 Sep 2022
Historique:
received:
30
08
2022
revised:
18
09
2022
accepted:
19
09
2022
entrez:
14
10
2022
pubmed:
15
10
2022
medline:
18
10
2022
Statut:
epublish
Résumé
Due to the heterogeneity of breast cancer, current available treatment options are moderately effective at best. Hence, it is highly recommended to comprehend different subtypes, understand pathogenic mechanisms involved, and develop treatment modalities. The repurposing of an old FDA approved anti-malarial drug, amodiaquine (AQ) presents an outstanding opportunity to explore its efficacy in treating majority of breast cancer subtypes. Cytotoxicity, scratch assay, vasculogenic mimicry study, and clonogenic assay were employed to determine AQ's ability to inhibit cell viability, cell migration, vascular formation, and colony growth. 3D Spheroid cell culture studies were performed to identify tumor growth inhibition potential of AQ in MCF-7 and MDAMB-231 cell lines. Apoptosis assays, cell cycle analysis, RT-qPCR assays, and Western blot studies were performed to determine AQ's ability to induce apoptosis, cell cycle changes, gene expression changes, and induction of autophagy marker proteins. The results from in-vitro studies confirmed the potential of AQ as an anti-cancer drug. In different breast cancer cell lines tested, AQ significantly induces cytotoxicity, inhibit colony formation, inhibit cell migration, reduces 3D spheroid volume, induces apoptosis, blocks cell cycle progression, inhibit expression of cancer related genes, and induces LC3BII protein to inhibit autophagy. Our results demonstrate that amodiaquine is a promising drug to repurpose for breast cancer treatment, which needs numerous efforts from further studies.
Identifiants
pubmed: 36232751
pii: ijms231911455
doi: 10.3390/ijms231911455
pmc: PMC9569809
pii:
doi:
Substances chimiques
Antimalarials
0
Antineoplastic Agents
0
Amodiaquine
220236ED28
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : National Heart Lung and Blood Institute
ID : 1R15HL138606-01A1
Déclaration de conflit d'intérêts
The authors declare no conflict of interest.
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