Melatonin, a Full Service Anti-Cancer Agent: Inhibition of Initiation, Progression and Metastasis.
Melatonin, a Full Service Anti-Cancer Agent: Inhibition of Initiation, Progression and Metastasis.
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DOI：
10.3390/ijms18040843
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发表时间：
2017-04-17
影响因子：
5.6
通讯作者：
Xu K
中科院分区：
文献类型：
--
作者：
Reiter RJ;Rosales-Corral SA;Tan DX;Acuna-Castroviejo D;Qin L;Yang SF;Xu K
有高度可信的证据表明，褪黑素在起始、进展和转移阶段减轻癌症。在许多情况下，已经提出了支持这些抑制作用的分子机制。然而，令人困惑的是，据报道，褪黑素通过大量的过程抑制癌症的发展和生长。这些不同的作用表明，所观察到的只是褪黑素潜在的更基本的作用的副现象，尚待披露。褪黑素对癌症的一些抑制作用显然是膜受体介导的，而另一些则是膜受体独立的，涉及这种无处不在的分子的直接细胞内作用。虽然褪黑素/癌症研究的重点一直放在吲哚胺在抑制乳腺癌中的作用上，但随着许多癌症类型被证明容易受到褪黑素的抑制，这种情况正在迅速改变。这项研究有几个方面可以在临床水平上立即应用。许多研究表明，与褪黑激素共同服用可以提高癌症对常规药物抑制的敏感性。更重要的发现是，褪黑素使以前完全抵抗治疗的癌症对同样的治疗变得敏感。褪黑素还通过限制癌细胞进入血管系统和防止它们在远处建立继发生长来抑制与转移相关的分子过程。这是特别重要的，因为癌症转移往往显著导致患者死亡。另一个值得进一步考虑的领域是褪黑素在减少抗癌药物毒性的同时提高其疗效方面的能力。虽然这些信息已经有十多年了，但在临床水平上还没有得到充分的利用。即使褪黑素对癌症患者的唯一有益作用是其减轻急性和长期药物毒性的能力，褪黑素也应用于改善患者的身体健康。然而，实验结果表明，将褪黑激素与传统癌症疗法联合使用的好处将远远超过对患者健康的改善。
There is highly credible evidence that melatonin mitigates cancer at the initiation, progression and metastasis phases. In many cases, the molecular mechanisms underpinning these inhibitory actions have been proposed. What is rather perplexing, however, is the large number of processes by which melatonin reportedly restrains cancer development and growth. These diverse actions suggest that what is being observed are merely epiphenomena of an underlying more fundamental action of melatonin that remains to be disclosed. Some of the arresting actions of melatonin on cancer are clearly membrane receptor-mediated while others are membrane receptor-independent and involve direct intracellular actions of this ubiquitously-distributed molecule. While the emphasis of melatonin/cancer research has been on the role of the indoleamine in restraining breast cancer, this is changing quickly with many cancer types having been shown to be susceptible to inhibition by melatonin. There are several facets of this research which could have immediate applications at the clinical level. Many studies have shown that melatonin’s co-administration improves the sensitivity of cancers to inhibition by conventional drugs. Even more important are the findings that melatonin renders cancers previously totally resistant to treatment sensitive to these same therapies. Melatonin also inhibits molecular processes associated with metastasis by limiting the entrance of cancer cells into the vascular system and preventing them from establishing secondary growths at distant sites. This is of particular importance since cancer metastasis often significantly contributes to death of the patient. Another area that deserves additional consideration is related to the capacity of melatonin in reducing the toxic consequences of anti-cancer drugs while increasing their efficacy. Although this information has been available for more than a decade, it has not been adequately exploited at the clinical level. Even if the only beneficial actions of melatonin in cancer patients are its ability to attenuate acute and long-term drug toxicity, melatonin should be used to improve the physical wellbeing of the patients. The experimental findings, however, suggest that the advantages of using melatonin as a co-treatment with conventional cancer therapies would far exceed improvements in the wellbeing of the patients.