Eugenol-Induced Autophagy and Apoptosis in Breast Cancer Cells via PI3K/AKT/FOXO3a Pathway Inhibition
| Autor: | Mohamed M. Hafez, Zeinab K. Hassan, Othman A. Al-Shabanah, Mashan L. Abdullah |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Cyclin-Dependent Kinase Inhibitor p21
autophagy Programmed cell death QH301-705.5 Antineoplastic Agents Apoptosis Breast Neoplasms Article Catalysis Inorganic Chemistry Phosphatidylinositol 3-Kinases chemistry.chemical_compound Cyclin-dependent kinase Cell Line Tumor Humans Biology (General) Physical and Theoretical Chemistry QD1-999 Molecular Biology Protein kinase B Spectroscopy PI3K/AKT/mTOR pathway Cell Proliferation Membrane Glycoproteins biology Chemistry Forkhead Box Protein O3 Organic Chemistry Autophagy General Medicine Computer Science Applications Nuclear Pore Complex Proteins Eugenol PI3K/AKT/FOXO3a pathway triple negative breast cancer Cancer cell Cancer research FOXO3 biology.protein Female Microtubule-Associated Proteins Proto-Oncogene Proteins c-akt eugenol Cyclin-Dependent Kinase Inhibitor p27 Signal Transduction |
| Zdroj: | International Journal of Molecular Sciences Volume 22 Issue 17 International Journal of Molecular Sciences, Vol 22, Iss 9243, p 9243 (2021) |
| ISSN: | 1422-0067 |
| DOI: | 10.3390/ijms22179243 |
| Popis: | The use of natural compounds is promising in approaches to prevent and treat cancer. The long-term application of most currently employed chemotherapy techniques has toxic side effects. Eugenol, a phenolic phytochemical extracted from certain essential oils, has an anti-cancer effect. The modulation of autophagy can promote either the survival or apoptosis of cancer cells. Triple-negative (MDA-MB-231) and HER2 positive (SK-BR-3) breast cancer cell lines were treated with different doses of eugenol. Apoptosis was detected by a flow-cytometry technique, while autophagy was detected by acridine orange. Real-time PCR and Western blot assays were applied to investigate the effect of eugenol on the gene and protein expression levels of autophagy and apoptotic genes. Treating cells with different concentrations of eugenol significantly inhibited cell proliferation. The protein levels of AKT serine/threonine kinase 1 (AKT), forkhead box O3 (FOXO3a), cyclin dependent kinase inhibitor 1A (p21), cyclin-dependent kinase inhibitor (p27), and Caspase-3 and -9 increased significantly in Eugenol-treated cells. Eugenol also induced autophagy by upregulating the expression levels of microtubule-associated protein 1 light chain 3 (LC3) and downregulating the expression of nucleoporin 62 (NU p62). Eugenol is a promising natural anti-cancer agent against triple-negative and HER2-positive breast cancer. It appears to work by targeting the caspase pathway and by inducing autophagic cell death. |
| Databáze: | OpenAIRE |
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