Melatonin enhances arsenic trioxide-induced cell death via sustained upregulation of Redd1 expression in breast cancer cells

Yun, Sun Hee; Woo, Seung Kyoon; Oh, Sang Taek; Hong, Sung Eun; Choe, Taeboo; Ye, Sang Kyu; Kim, Eun Kyu; Seong, Min Ki; Kim, Hyun A.; Noh, Woo Chul; Lee, Jin Kyung; Jin, Hyeon Ok; Lee, Yun Han; Park, In-Cheol

doi:10.1016/j.mce.2015.11.016

Cited by 57 publications

(47 citation statements)

References 35 publications

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“…Corresponding effects by melatonin are not sufficiently documented. A single paper reported inhibition of mTORC1 signaling in hepatoma, whereas other studies in squamous cell carcinoma and breast cancer rather indicated a promotion of mTORC1 signaling by melatonin, however, under concomitant oncostatic treatment . To definitely judge the role of melatonin in this pathway, it would be important to investigate this under exclusively inflammatory conditions, in the absence of co‐medication.…”

Section: Downstream Factors Of Melatonin's Actions With Relevance To mentioning

confidence: 99%

Melatonin and inflammation—Story of a double‐edged blade

Hardeland

2018

Journal of Pineal Research

363

350

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Melatonin is an immune modulator that displays both pro‐ and anti‐inflammatory properties. Proinflammatory actions, which are well documented by many studies in isolated cells or leukocyte‐derived cell lines, can be assumed to enhance the resistance against pathogens. However, they can be detrimental in autoimmune diseases. Anti‐inflammatory actions are of particular medicinal interest, because they are observed in high‐grade inflammation such as sepsis, ischemia/reperfusion, and brain injury, and also in low‐grade inflammation during aging and in neurodegenerative diseases. The mechanisms contributing to anti‐inflammatory effects are manifold and comprise various pathways of secondary signaling. These include numerous antioxidant effects, downregulation of inducible and inhibition of neuronal NO synthases, downregulation of cyclooxygenase‐2, inhibition of high‐mobility group box‐1 signaling and toll‐like receptor‐4 activation, prevention of inflammasome NLRP3 activation, inhibition of NF‐κB activation and upregulation of nuclear factor erythroid 2‐related factor 2 (Nrf2). These effects are also reflected by downregulation of proinflammatory and upregulation of anti‐inflammatory cytokines. Proinflammatory actions of amyloid‐β peptides are reduced by enhancing α‐secretase and inhibition of β‐ and γ‐secretases. A particular role in melatonin's actions seems to be associated with the upregulation of sirtuin‐1 (SIRT1), which shares various effects known from melatonin and additionally interferes with the signaling by the mechanistic target of rapamycin (mTOR) and Notch, and reduces the expression of the proinflammatory lncRNA‐CCL2. The conclusion on a partial mediation by SIRT1 is supported by repeatedly observed inhibitions of melatonin effects by sirtuin inhibitors or knockdown.

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Section: Downstream Factors Of Melatonin's Actions With Relevance To mentioning

confidence: 99%

Melatonin and inflammation—Story of a double‐edged blade

Hardeland

2018

Journal of Pineal Research

363

350

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“…For example, melatonin further stimulated apoptotic cell death promoted by arsenic trioxide; this involved an augmented production of intracellular ROS, upregulation of Redd1 expression and an activation of the p38/JNK (c-JUN-N-terminal kinase) pathway in human breast cancer cells [218]. Likewise, when combined with puromycin, melatonin synergistically had an inhibitory effect on MDA-MB 231 breast cancer cells; this included a reduction in the expression of 45S pre-rRNA while a downregulation of upstream binding factors XPO1 and IPO7, procaspase 3 and Bcl-xl [219].…”

Section: Melatonin and Cancer Progressionmentioning

confidence: 99%

Melatonin, a Full Service Anti-Cancer Agent: Inhibition of Initiation, Progression and Metastasis

Reíter

Rosales-Corral

Tan

et al. 2017

IJMS

377

368

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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.

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“…Melatonin enhanced the effects of doxorubicin by activating transient receptor potential vanilloid 1 (TRPV1) and apoptosis as well as inducing MCF-7 cell death [74]. In addition, melatonin enhanced the apoptotic cell death induced by arsenic trioxide via ROS generation, upregulation of Redd1 expression, and activation of the p38/JNK pathways in human breast cancer cells [75]. Besides, melatonin (3 mM) combined with puromycin (1 μM) exerted synergistically inhibitory effect on MDA-MB 231 cells, through attenuating the expression of 45S pre-rRNA and upstream binding factor, and downregulating upstream binding factor, XPO1 and IPO7, procaspase 3, and Bcl-xL [76].…”

Section: Experimental Studiesmentioning

confidence: 99%

Melatonin for the prevention and treatment of cancer

et al. 2017

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The epidemiological studies have indicated a possible oncostatic property of melatonin on different types of tumors. Besides, experimental studies have documented that melatonin could exert growth inhibition on some human tumor cells in vitro and in animal models. The underlying mechanisms include antioxidant activity, modulation of melatonin receptors MT1 and MT2, stimulation of apoptosis, regulation of pro-survival signaling and tumor metabolism, inhibition on angiogenesis, metastasis, and induction of epigenetic alteration. Melatonin could also be utilized as adjuvant of cancer therapies, through reinforcing the therapeutic effects and reducing the side effects of chemotherapies or radiation. Melatonin could be an excellent candidate for the prevention and treatment of several cancers, such as breast cancer, prostate cancer, gastric cancer and colorectal cancer. This review summarized the anticancer efficacy of melatonin, based on the results of epidemiological,experimental and clinical studies, and special attention was paid to the mechanisms of action.

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Melatonin enhances arsenic trioxide-induced cell death via sustained upregulation of Redd1 expression in breast cancer cells

Cited by 57 publications

References 35 publications

Melatonin and inflammation—Story of a double‐edged blade

Melatonin and inflammation—Story of a double‐edged blade

Melatonin, a Full Service Anti-Cancer Agent: Inhibition of Initiation, Progression and Metastasis

Melatonin for the prevention and treatment of cancer

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