Eugenol-Induced Autophagy and Apoptosis in Breast Cancer Cells via PI3K/AKT/FOXO3a Pathway Inhibition
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...
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MDPI AG
2021-08-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/17/9243 |
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| author | Mashan L. Abdullah Othman Al-Shabanah Zeinab K. Hassan Mohamed M. Hafez |
| author_facet | Mashan L. Abdullah Othman Al-Shabanah Zeinab K. Hassan Mohamed M. Hafez |
| author_sort | Mashan L. Abdullah |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-10T08:11:51Z |
| format | Article |
| id | doaj.art-96bbde03a96e42dfa03223bdebe9a60e |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T08:11:51Z |
| publishDate | 2021-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-96bbde03a96e42dfa03223bdebe9a60e2023-11-22T10:40:33ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-08-012217924310.3390/ijms22179243Eugenol-Induced Autophagy and Apoptosis in Breast Cancer Cells via PI3K/AKT/FOXO3a Pathway InhibitionMashan L. Abdullah0Othman Al-Shabanah1Zeinab K. Hassan2Mohamed M. Hafez3Experimental Medicine Department, King Abdullah International Medical Research Center, King Saud bin Abdulaziz University for Health Sciences, MNGHA, Riyadh 11426, Saudi ArabiaPharmacology and Toxicology Department, King Saud University, Riyadh 11426, Saudi ArabiaCancer Biology Department, National Cancer Institute, Cairo University, Cairo 12613, EgyptCancer Biology Department, National Cancer Institute, Cairo University, Cairo 12613, EgyptThe 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.https://www.mdpi.com/1422-0067/22/17/9243eugenoltriple negative breast cancerautophagyPI3K/AKT/FOXO3a pathway |
| spellingShingle | Mashan L. Abdullah Othman Al-Shabanah Zeinab K. Hassan Mohamed M. Hafez Eugenol-Induced Autophagy and Apoptosis in Breast Cancer Cells via PI3K/AKT/FOXO3a Pathway Inhibition International Journal of Molecular Sciences eugenol triple negative breast cancer autophagy PI3K/AKT/FOXO3a pathway |
| title | Eugenol-Induced Autophagy and Apoptosis in Breast Cancer Cells via PI3K/AKT/FOXO3a Pathway Inhibition |
| title_full | Eugenol-Induced Autophagy and Apoptosis in Breast Cancer Cells via PI3K/AKT/FOXO3a Pathway Inhibition |
| title_fullStr | Eugenol-Induced Autophagy and Apoptosis in Breast Cancer Cells via PI3K/AKT/FOXO3a Pathway Inhibition |
| title_full_unstemmed | Eugenol-Induced Autophagy and Apoptosis in Breast Cancer Cells via PI3K/AKT/FOXO3a Pathway Inhibition |
| title_short | Eugenol-Induced Autophagy and Apoptosis in Breast Cancer Cells via PI3K/AKT/FOXO3a Pathway Inhibition |
| title_sort | eugenol induced autophagy and apoptosis in breast cancer cells via pi3k akt foxo3a pathway inhibition |
| topic | eugenol triple negative breast cancer autophagy PI3K/AKT/FOXO3a pathway |
| url | https://www.mdpi.com/1422-0067/22/17/9243 |
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