ArticleExperimental & molecular medicine2021
Melatonin and doxorubicin synergistically enhance apoptosis via autophagy-dependent reduction of AMPKα1 transcription in human breast cancer cells.
Article in Experimental & molecular medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 35 citations in OpenAlex.
- Nutritional Prevention of Oxidative Stress-Induced Cardiotoxicity in Pediatric Cardio-Oncology: Molecular Mechanisms and Translational Perspectives-A Narrative Review.International journal of molecular sciences · 2026Review
- Inhibitory Effect of Melatonin on the Proliferation of Breast Cancer Cells MDA-MB-468 by Antioxidants Superoxide Dismutase and Glutathione Peroxidase.Asian Pacific journal of cancer prevention : APJCP · 2026Article
- Targeting kinases that regulate programmed cell death: a new therapeutic strategy for breast cancer.Journal of translational medicine · 2025Review
- Multifaced Anticancer Potential of Doxorubicin: Spotlight on Breast Cancer.Diseases & research · 2025Article
- Small Extracellular Vesicles from Breast Cancer Cells Induce Cardiotoxicity.International journal of molecular sciences · 2025Article
- Melatonin combined with antineoplastic drugs or natural products for cancer treatment: An update.Current research in pharmacology and drug discovery · 2025Review
- Article
- miRNAs as short non-coding RNAs in regulating doxorubicin resistance.Journal of cell communication and signaling · 2023Review
- Melatonin blunted the angiogenic activity in 3D colon cancer tumoroids by the reduction of endocan.Cancer cell international · 2023Article
- Therapeutic Potential of Melatonin Counteracting Chemotherapy-Induced Toxicity in Breast Cancer Patients: A Systematic Review.Pharmaceutics · 2023Review
- Recent Developments in Combination Chemotherapy for Colorectal and Breast Cancers with Topoisomerase Inhibitors.International journal of molecular sciences · 2023Review
- Potential Roles of Melatonin in Doxorubicin-Induced Cardiotoxicity: From Cellular Mechanisms to Clinical Application.Pharmaceutics · 2023Review
- microRNA-130b-3p Attenuates Septic Cardiomyopathy by Regulating the AMPK/mTOR Signaling Pathways and Directly Targeting ACSL4 against Ferroptosis.International journal of biological sciences · 2023Article
- A Hydrodistillate ofNutrients · 2022Article
- Pro-Apoptotic and Anti-Migration Properties of a Thiazoline-Containing Platinum(II) Complex in MDA-MB-231 Breast Cancer Cells: The Role of Melatonin as a Synergistic Agent.Antioxidants (Basel, Switzerland) · 2022Article
- Dual Effect of Tryptamine on Prostate Cancer Cell Growth Regulation: A Pilot Study.International journal of molecular sciences · 2022Article
- Hybrid Fluorescent Mass-Tag Nanotrackers as Universal Reagents for Long-Term Live-Cell Barcoding.Analytical chemistry · 2022Article
- Use of Melatonin in Cancer Treatment: Where Are We?International journal of molecular sciences · 2022Review
- Targeting Breast Cancer and Their Stem Cell Population through AMPK Activation: Novel Insights.Cells · 2022Review
- Effects of Modified Melatonin Release on Human Colostrum Neutrophils to Induce Death in the MCF-7 Cell Line.International journal of cell biology · 2022Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Doxorubicin is one of the most effective agents used to treat various cancers, including breast cancer, but its usage is limited by the risk of adverse effects, including cardiotoxicity. Melatonin, a natural hormone that functions as a major regulator of circadian rhythms, has been considered a supplemental component for doxorubicin due to its potential to improve its effectiveness. However, the mechanisms and biological targets of the combination of melatonin and doxorubicin with respect to cancer cell death are not well understood. In the present study, we found that melatonin synergized with doxorubicin to induce apoptosis of breast cancer cells by decreasing the expression of AMP-activated protein kinase α1 (AMPK α1), which acts as a critical survival factor for cancer cells. This cotreatment-induced reduction in AMPKα1 expression occurred at the transcriptional level via an autophagy-dependent mechanism. The synergistic effects of the combined treatment were evident in many other cancer cell lines, and melatonin was also highly effective in inducing cancer death when combined with other cancer drugs, including cisplatin, 5-fluorouracil, irinotecan, and sorafenib. AMPKα1 expression was decreased in all of these cases, suggesting that reducing AMPKα1 can be considered an effective method to increase the sensitivity of cancer cells to doxorubicin treatment.
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