{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T16:53:46Z","timestamp":1787504026308,"version":"build-2736575974"},"reference-count":58,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2012,4,27]],"date-time":"2012-04-27T00:00:00Z","timestamp":1335484800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Pineal Research"],"published-print":{"date-parts":[[2012,11]]},"abstract":"<jats:p>\n                    <jats:bold>Abstract:\u2002<\/jats:bold>\n                    Melatonin is an indolamine that is synthesized in the pineal gland and shows a wide range of physiological functions. Although the anti\u2010aging properties of melatonin have been reported in a senescence\u2010accelerated mouse model, whether melatonin modulates cellular senescence has not been determined. In this study, we examined the effect of melatonin on anticancer drug\u2010induced cellular premature senescence. We found that the doxorubicin (DOX)\u2010induced senescence of A549 human lung cancer cells and IMR90 normal lung cells was substantially inhibited by cotreatment with melatonin in a dose\u2010dependent manner. Mechanistically, the DOX\u2010induced G2\/M phase cell cycle arrest and the decrease in cyclinB and cdc2 expression were not affected by melatonin. However, the DOX\u2010induced increase in intracellular levels of ROS, which is necessary for premature senescence, was completely abolished upon melatonin cotreatment. In addition, the reduction in mitochondrial membrane potential that occurs upon DOX treatment was inhibited by melatonin. An aberrant increase in mitochondrial respiration was also significantly suppressed by melatonin, indicating that melatonin ameliorates the mitochondrial dysfunction induced by DOX treatment. The treatment of A549 cells with luzindole, a potent inhibitor of melatonin receptors, failed to prevent the effects of melatonin treatment on mitochondrial functions and premature senescence in cells also treated with DOX; this suggests that melatonin suppresses DOX\u2010induced senescence in a melatonin receptor\u2010independent manner. Together, these results reveal that melatonin has an inhibitory effect of melatonin on premature senescence at the cellular level and that melatonin protects A549 cells from DOX\u2010induced senescence. Thus, melatonin might have the therapeutic potential to prevent the side effects of anticancer drug therapy.\n                  <\/jats:p>","DOI":"10.1111\/j.1600-079x.2012.01003.x","type":"journal-article","created":{"date-parts":[[2012,4,4]],"date-time":"2012-04-04T10:32:50Z","timestamp":1333535570000},"page":"335-343","source":"Crossref","is-referenced-by-count":44,"title":["Melatonin suppresses doxorubicin\u2010induced premature senescence of A549 lung cancer cells by ameliorating mitochondrial dysfunction"],"prefix":"10.1111","volume":"53","author":[{"given":"Naree","family":"Song","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ae Jeong","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyun\u2010Ju","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hye 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