Department of Cell Systems and Anatomy, UT Health San Antonio, San Antonio, TX 78229, USA.
Department of Cell Systems and Anatomy, UT Health San Antonio, San Antonio, TX 78229, USA.
Life Sci. 2021 Aug 1;278:119597. doi: 10.1016/j.lfs.2021.119597. Epub 2021 May 8.
This brief review describes the association of the endogenous pineal melatonin rhythm with the metabolic flux of solid tumors, particularly breast cancer. It also summarizes new information on the potential mechanisms by which endogenously-produced or exogenously-administered melatonin impacts the metabolic phenotype of cancer cells. The evidence indicates that solid tumors may redirect their metabolic phenotype from the pathological Warburg-type metabolism during the day to the healthier mitochondrial oxidative phosphorylation on a nightly basis. Thus, they function as cancer cells only during the day and as healthier cells at night, that is, they are only part-time cancerous. This switch to oxidative phosphorylation at night causes cancer cells to exhibit a reduced tumor phenotype and less likely to rapidly proliferate or to become invasive or metastatic. Also discussed is the likelihood that some solid tumors are especially aggressive during the day and much less so at night due to the nocturnal rise in melatonin which determines their metabolic state. We further propose that when melatonin is used/tested in clinical trials, a specific treatment paradigm be used that is consistent with the temporal metabolic changes in tumor metabolism. Finally, it seems likely that the concurrent use of melatonin in combination with conventional chemotherapies also would improve cancer treatment outcomes.
这篇简短的综述描述了内源性松果腺褪黑素节律与实体瘤（特别是乳腺癌）代谢通量的关联。它还总结了内源性或外源性褪黑素影响癌细胞代谢表型的潜在机制的新信息。有证据表明，实体瘤可能会将其代谢表型从白天的病理性瓦堡型代谢重定向到夜间更健康的线粒体氧化磷酸化。因此，它们仅在白天作为癌细胞发挥作用，而在夜间作为更健康的细胞发挥作用，也就是说，它们只是兼职的癌细胞。这种夜间向氧化磷酸化的转变导致癌细胞表现出降低的肿瘤表型，不太可能快速增殖或变得侵袭性或转移性。此外，还讨论了由于夜间褪黑素的升高决定了它们的代谢状态，某些实体瘤在白天尤其具有侵袭性，而在夜间则不那么具有侵袭性的可能性。我们进一步提出，当褪黑素在临床试验中被使用/测试时，应该使用一种与肿瘤代谢的时间代谢变化一致的特定治疗模式。最后，似乎同时使用褪黑素与常规化疗也可以改善癌症治疗效果。
