Combination of Pitavastatin and melatonin shows partial antineoplastic effects in a rat breast carcinoma model

Kubatka, Peter; Bojková, Bianka; Kassayová, Monika; Orendáš, Peter; Kajo, Karol; Výbohová, Desanka; Kružliak, Peter; Adamicová, Katarína; Péč, Martin; Stollárová, Nadežda; Adamkov, Marián

doi:10.1016/j.acthis.2014.09.010

Cited by 27 publications

(12 citation statements)

References 38 publications

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“…267 Statins reportedly have additional benefits including oncostatic actions and antifibrillating and defibrillating potential. Melatonin was found to exaggerate the cancer-inhibiting actions of pitavastatin 268 and pravastatin 269 against breast cancer in experimental studies. Melatonin also has antiarrhythmic potential equivalent to that of atorvastatin in an isolated heart model.…”

Section: F I G U R Ementioning

confidence: 99%

Melatonin as an antioxidant: under promises but over delivers

Reíter

Mayo

Tan

et al. 2016

Journal of Pineal Research

1,271

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Melatonin is uncommonly effective in reducing oxidative stress under a remarkably large number of circumstances. It achieves this action via a variety of means: direct detoxification of reactive oxygen and reactive nitrogen species and indirectly by stimulating antioxidant enzymes while suppressing the activity of pro-oxidant enzymes. In addition to these well-described actions, melatonin also reportedly chelates transition metals, which are involved in the Fenton/Haber-Weiss reactions; in doing so, melatonin reduces the formation of the devastatingly toxic hydroxyl radical resulting in the reduction of oxidative stress. Melatonin's ubiquitous but unequal intracellular distribution, including its high concentrations in mitochondria, likely aid in its capacity to resist oxidative stress and cellular apoptosis. There is credible evidence to suggest that melatonin should be classified as a mitochondria-targeted antioxidant. Melatonin's capacity to prevent oxidative damage and the associated physiological debilitation is well documented in numerous experimental ischemia/ reperfusion (hypoxia/reoxygenation) studies especially in the brain (stroke) and in the heart (heart attack). Melatonin, via its antiradical mechanisms, also reduces the toxicity of noxious prescription drugs and of methamphetamine, a drug of abuse.Experimental findings also indicate that melatonin renders treatment-resistant cancers sensitive to various therapeutic agents and may be useful, due to its multiple antioxidant actions, in especially delaying and perhaps treating a variety of agerelated diseases and dehumanizing conditions. Melatonin has been effectively used to combat oxidative stress, inflammation and cellular apoptosis and to restore tissue function in a number of human trials; its efficacy supports its more extensive use in a wider variety of human studies. The uncommonly high-safety profile of melatonin also bolsters this conclusion. It is the current feeling of the authors that, in view of the widely diverse beneficial functions that have been reported for melatonin, these may be merely epiphenomena of the more fundamental, yet-to-be identified basic action(s) of this ancient molecule. K E Y W O R D Sdiseases of aging, drug toxicity, free radicals, ischemia/reperfusion, mitochondria-targeted antioxidant, organ transplantation, statins

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Section: F I G U R Ementioning

confidence: 99%

Melatonin as an antioxidant: under promises but over delivers

Reíter

Mayo

Tan

et al. 2016

Journal of Pineal Research

1,271

1,040

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“…In one study a combination consisting of melatonin and Propionibacterium acnes showed reduction in VEGF serum levels and regression in tumor size in mice bearing breast carcinoma [ 27 ]. Additionally, combination of melatonin with pitvastatin caused 42% reduction in the levels of VEGF in the combination group compared with pitvastatin single therapy in rats with breast cancer [ 121 ].…”

Section: Melatonin and Cancer Hallmarksmentioning

confidence: 99%

Melatonin and Cancer Hallmarks

2018

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Melatonin is a natural indoleamine produced by the pineal gland that has many functions, including regulation of the circadian rhythm. Many studies have reported the anticancer effect of melatonin against a myriad of cancer types. Cancer hallmarks include sustained proliferation, evading growth suppressors, metastasis, replicative immortality, angiogenesis, resisting cell death, altered cellular energetics, and immune evasion. Melatonin anticancer activity is mediated by interfering with various cancer hallmarks. This review summarizes the anticancer role of melatonin in each cancer hallmark. The studies discussed in this review should serve as a solid foundation for researchers and physicians to support basic and clinical studies on melatonin as a promising anticancer agent.

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“…The pineal hormone administered by subcutaneous injection (500 μ g daily, 1 h before darkness, 20 weeks) potentiated the tumor prevention by 9-cis-retinoic [ 172 ]. At 20 mg/ml added in the water (7 days prior to the carcinogen, administered during 15 weeks), melatonin potentiated the antitumor effect of statins [ 55 , 173 ].…”

Section: Melatonin Influences Breast Prostate and Ovary Cancer Amentioning

confidence: 99%

Melatonin: An Anti-Tumor Agent in Hormone-Dependent Cancers

Menéndez-Menéndez

Martínez‐Campa

2018

International Journal of Endocrinology

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Melatonin (N-acetyl-5-methoxytryptamine) is a hormone synthesized and secreted by the pineal gland mainly during the night, since light exposure suppresses its production. Initially, an implication of this indoleamine in malignant disease was described in endocrine-responsive breast cancer. Data from several clinical trials and multiple experimental studies performed both in vivo and in vitro have documented that the pineal hormone inhibits endocrine-dependent mammary tumors by interfering with the estrogen signaling-mediated transcription, therefore behaving as a selective estrogen receptor modulator (SERM). Additionally, melatonin regulates the production of estradiol through the control of the enzymes involved in its synthesis, acting as a selective estrogen enzyme modulator (SEEM). Many more mechanisms have been proposed during the past few years, including signaling triggered after activation of the membrane melatonin receptors MT-1 and MT-2, or else intracellular actions targeting molecules such as calmodulin, or binding intranuclear receptors. Similar results have been obtained in prostate (regulation of enzymes involved in androgen synthesis and modulation of androgen receptor levels and activity) and ovary cancer. Thus, tumor metabolism, gene expression, or epigenetic modifications are modulated, cell growth is impaired and angiogenesis and metastasis are inhibited. In the last decade, many more reports have demonstrated that melatonin is a promising adjuvant molecule with many potential beneficial consequences when included in chemotherapy or radiotherapy protocols designed to treat endocrine-responsive tumors. Therefore, in this state-of-the-art review, we aim to compile the knowledge about the oncostatic actions of the indoleamine in hormone-dependent tumors, and the latest findings concerning melatonin actions when administered in combination with radio- or chemotherapy in breast, prostate, and ovary cancers. As melatonin has no toxicity, it may be well deserve to be considered as an endogenously generated agent helpful in cancer prevention and treatment.

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Combination of Pitavastatin and melatonin shows partial antineoplastic effects in a rat breast carcinoma model

Cited by 27 publications

References 38 publications

Melatonin as an antioxidant: under promises but over delivers

Melatonin as an antioxidant: under promises but over delivers

Melatonin and Cancer Hallmarks

Melatonin: An Anti-Tumor Agent in Hormone-Dependent Cancers

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