ReferenceID 5741

Melatonin and doxorubicin synergistically enhance apoptosis via autophagy-dependent reduction of AMPKα1 transcription in human breast cancer cells

Exp Mol Med

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

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Reference Id
5741
Evidence Id
22331
Core Evidence Id
22331
Source Reference Id
4720
Herb2 Reference Id
HBREF005517
Subject Paper Key
HBIN034657_34584194
Pubmed Id
34584194
Doi
10.1038/s12276-021-00675-y
Paper Title
Melatonin and doxorubicin synergistically enhance apoptosis via autophagy-dependent reduction of AMPKα1 transcription in human breast cancer cells
Paper 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 alpha1 (AMPK alpha1), which acts as a critical survival factor for cancer cells. This cotreatment-induced reduction in AMPKalpha1 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. AMPKalpha1 expression was decreased in all of these cases, suggesting that reducing AMPKalpha1 can be considered an effective method to increase the sensitivity of cancer cells to doxorubicin treatment.
Journal
Exp Mol Med
Publish Year
2021
Experiment Subject
Experiment Type
Cell Experiment
Phenotype Related
Cardiotoxicity; Cancers; Cancer; Breast Cancer
Paper Title Cn
Paper Title En
Melatonin and doxorubicin synergistically enhance apoptosis via autophagy-dependent reduction of AMPKα1 transcription in human breast cancer cells
Bilingual Status
semi_complete