Melatonin, an inhibitory agent in breast cancer

Nooshinfar, Elaheh; Safaroghli‐Azar, Ava; Bashash, Davood; Akbari, Mohammad Esmaeil

doi:10.1007/s12282-016-0690-7

Cited by 80 publications

(58 citation statements)

References 72 publications

(124 reference statements)

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“…Melatonin, including at physiological concentrations (1 nM) exerts cytotoxic, anti-mitotic and pro-apoptotic actions in these cells [40,202,203]. That melatonin has antiproliferative functions have been validated in both ERα-positive and ERα-negative human breast cancer cell lines [179,204].…”

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

376

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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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

376

368

View full text Add to dashboard Cite

show abstract

“…12 The indoleamine has great pharmacological promise as an antioxidant enzyme that can scavenge free radicals, and protect from oxidative damage. 13,14 Previous studies has shown that melatonin can inhibit the proliferation of various human cancers, including leukemia, 15,16 hepatocarcinoma, 17 breast cancer, 18 colorectal cancer, 19,20 lung cancer, 21,22 and gastric carcinoma. 23,24 However, studies investigating the molecular link between the UPR and autophagy activation by melatonin in GC are sparse.…”

Section: Introductionmentioning

confidence: 99%

<p>The Therapeutic Effect of Melatonin on GC by Inducing Cell Apoptosis and Autophagy Induced by Endoplasmic Reticulum Stress</p>

Zheng¹,

Tu²,

Wang³

et al. 2019

OTT

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Background: Gastric cancer (GC) is the main malignancy affecting a large population worldwide. Lack of effective enough treatment is one of the leading factors contributing to the high mortality rate. Melatonin, a naturally occurring compound, has been proven to exert cytotoxic and antiproliferative effects on human gastric cancers. Nevertheless, the mechanisms of anti-gastric cancer of melatonin remain elucidated. It is believed that endoplasmic reticulum (ER) stress and its resultant unfolded protein response (UPR) are connected to the survival, progression, and chemoresistance of various tumor cells via multiple cellular procedures, such as autophagy. In this study, the effects of melatonin on human gastric cancer cell lines AGS and SGC-7901 was assessed to reveal the interaction between melatonin, endoplasmic reticulum stress, and autophagy in gastric cancer. Methods: CCK-8, the wound healing analysis, colony formation assay, immunofluorescence analysis, Western blotting, flow cytometry, and animal models were used in the current study. Results: The data demonstrated that melatonin could inhibit GC growth, proliferation, and invasion both in vivo and in vitro. Apoptosis and autophagy induced in a concentrationdependent manner is response to melatonin-induced ER stress. Melatonin induced the expression of apoptotic and autophagy-related proteins, which was markedly attenuated by the ER stress inhibitor 4-PBA and autophagy inhibitor 3-MA. In addition, we used the specific IRE1 inhibitor STF 083010, finding that inhibiting IRE1 could considerably relieve ER stress-induced autophagy activity, as revealed by the reduction of LC3-II and Beclin-1. Conclusion: This study confirmed that melatonin-induced inhibition of GC cell proliferation is mediated by the activation of the IRE/JNK/Beclin1 signaling.

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“…Melatonin (MT) has been shown to function as an antiestrogenic agent, and only for this reason should be considered for BC treatment [217,221] (Table 2). Sonehara et al, have shown that treatment with MT modulates tumor aggressiveness, increasing apoptosis under microenvironmental acidosis in BC cell lines [222].…”

Section: ) Hydrogen Ion Dynamics In Multiple Drug Resistance (Mdr) Imentioning

confidence: 99%

A New and Integral Approach to the Etiopathogenesis and Treatment of Breast Cancer based upon its Hydrogen Ion Dynamics

Harguindey¹,

Alfarouk

Orozco³

et al. 2019

Preprint

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Despite all efforts, the treatment of breast cancer (BC) cannot be considered to be a success story. The advances in surgery, chemotherapy and radiotherapy have not been sufficient. Indeed, the accumulated experience clearly indicates that new perspectives and non-main stream approaches are needed to better characterize the etiopathogenesis and treatment of this disease. This contibution deals with how the new pH-centric anticancer paradigm plays a fundamental role in reaching a more integral understanding of the etiology, etiopathogenesis and treatment of this multifactorial disease. For the first time the armamentarium available for the treatment of the different types and phases of BC is approached here from a Unitarian perspective based upon the hydrogen ion dynamics of cancer. The wide-ranged pH-related molecular, biochemical and metabolic model is able to embrace most the fields and subfields of breast cancer pathology. This single and integrated approach allows to advance a unidirectional program to treatment. Further efforts in this line are likely to first improve the therapeutics of each subtype of this tumor, then every phase of the disease and finally every individual patient.

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Melatonin, an inhibitory agent in breast cancer

Abstract: The broad inhibitory effects of melatonin in breast cancer make it a promising agent and may add it to the list of potential drugs in treatment of this cancer.

Cited by 80 publications

References 72 publications

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

<p>The Therapeutic Effect of Melatonin on GC by Inducing Cell Apoptosis and Autophagy Induced by Endoplasmic Reticulum Stress</p>

A New and Integral Approach to the Etiopathogenesis and Treatment of Breast Cancer based upon its Hydrogen Ion Dynamics

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