Epoxyazadiradione induced apoptosis/anoikis in triple-negative breast cancer cells, MDA-MB-231, by modulating diverse cellular effects
| Autor: | Sulochana Priya, Sreerenjini Lakshmi, Somappa B Sasidhar, Jalaja Renjitha |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Limonins Programmed cell death Health Toxicology and Mutagenesis Triple Negative Breast Neoplasms Toxicology Biochemistry Metastasis 03 medical and health sciences 0302 clinical medicine Downregulation and upregulation medicine Humans Anoikis Molecular Biology Triple-negative breast cancer 030102 biochemistry & molecular biology Chemistry Cancer General Medicine medicine.disease Neoplasm Proteins G2 Phase Cell Cycle Checkpoints Gene Expression Regulation Neoplastic Apoptosis 030220 oncology & carcinogenesis Cancer research Molecular Medicine M Phase Cell Cycle Checkpoints Female Cyclin A2 |
| Zdroj: | Journal of biochemical and molecular toxicologyREFERENCES. 35(6) |
| ISSN: | 1099-0461 |
| Popis: | Triple-negative breast cancer (TNBC) is one of the most aggressive forms of its kind, which accounts for 15-20% of all breast cancers. As this cancer form lacks hormone receptors, targeted chemotherapy remains the best treatment option. Apoptosis and anoikis (detachment-induced cell death) induction by small molecules can prevent TNBC metastasis to a greater extent. Epoxyazadiradione (EAD) is a limonoid from the neem plant with an anticancer property. Here, we demonstrate that EAD induced mitochondria-mediated apoptosis and anoikis in TNBC cells (MDA-MB-231). Apart from this, it promotes antimigration, inhibition of colony formation, downregulation of MMP-9 and fibronectin, induction of G2/M phase arrest with downregulation of cyclin A2/cdk2, interference in cellular metabolism, and inhibition of nuclear factor kappa-B (NF- kB) nuclear translocation. Moreover, a significant reduction is observed in the expression of EGFR on the plasma membrane and nucleus upon treatment with EAD. Among the diverse cellular effects, anoikis induction, metabolic interference, and downregulation of membrane/nuclear EGFR expression by EAD are reported here for the first time. To summarize, EAD targets multiple cellular events to induce growth arrest in TNBC, and hence can be developed into the best antineoplastic agent in the future. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Plný text