Melatonin enhances the apoptotic effects and modulates the changes in gene expression induced by docetaxel in MCF‑7 human breast cancer cells

Alonso‐González, Carolina; Menéndez-Menéndez, Javier; González-González, Alicia; González, Alicia; Cos, Samuel; Martínez‐Campa, Carlos

doi:10.3892/ijo.2017.4213

Cited by 40 publications

(44 citation statements)

References 56 publications

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“…Besides, pretreatment with the pineal hormone further stimulates the inhibition of cell proliferation exerted by docetaxel and vinorelbine. This finding matches with previous results of our group: melatonin enhances apoptosis, further represses cell proliferation and is able to alter the modifications in gene expression triggered by docetaxel in the estrogen-responsive MCF-7 cell line 34 . The next stage of angiogenesis we tested was cellular migration.…”

Section: Discussionsupporting

confidence: 93%

“…Combined with classical chemotherapeutic agents, melatonin enhances the efficacy of these drugs in breast cancer patients via a variety of mechanisms, including the capability of impairing angiogenesis 21,22,27,34 . Thus, in www.nature.com/scientificreports www.nature.com/scientificreports/ the present study, we analysed the effects of docetaxel and vinorelbine at different stages of angiogenesis, comparing the efficacy of the drugs alone or added together with the pineal hormone.…”

Section: Discussionmentioning

confidence: 99%

“…Each RT 2 Profiler PCR array plate also includes controls for data normalization, genomic DNA contamination detection, RNA sample quality and general PCR performance. As in previous works 34 , HUVECs, which have been treated for a week with melatonin 1 mM, were cultured into 60 × 15 mm plates in VCBM supplemented with 2% FBS and incubated at 37 °C for 24 h to allow for cell attachment. Then media were replaced by fresh ones with 2% FBS and containing either docetaxel (1 µM) or vinorelbine (1 µM) alone or in combination with 1 mM melatonin and/or vehicle (ethanol at a final concentration lower than 0.0001%).…”

Section: Measurement Of 17β-hydroxysteroid Dehydrogenase Typementioning

confidence: 99%

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Usefulness of melatonin as complementary to chemotherapeutic agents at different stages of the angiogenic process

González-González

González

Rueda

et al. 2020

Sci Rep

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chemotherapeutics are sometimes administered with drugs, like antiangiogenic compounds, to increase their effectiveness. Melatonin exerts antitumoral actions through antiangiogenic actions. We studied if melatonin regulates the response of HUVECs to chemotherapeutics (docetaxel and vinorelbine). The inhibition that these agents exert on some of the processes involved in angiogenesis, such as, cell proliferation, migratory capacity or vessel formation, was enhanced by melatonin. Regarding to estrogen biosynthesis, melatonin impeded the negative effect of vinorelbine, by decreasing the activity and expression of aromatase and sulfatase. Docetaxel and vinorelbine increased the expression of VEGF-A, VEGF-B, VEGF-C, VEGFR-1, VEGFR-3, ANG1 and/or ANG-2 and melatonin inhibited these actions. Besides, melatonin prevented the positive actions that docetaxel exerts on the expression of other factors related to angiogenesis like JAG1, ANPEP, IGF-1, CXCL6, AKT1, ERK1, ERK2, MMP14 and NOS3 and neutralized the stimulating actions of vinorelbine on the expression of FIGF, FGFR3, CXCL6, CCL2, ERK1, ERK2, AKT1, NOS3 and MMP14. In CAM assay melatonin inhibited new vascularization in combination with chemotherapeutics. Melatonin further enhanced the chemotherapeutics-induced inhibition of p-AKt and p-eRK and neutralized the chemotherapeuticscaused stimulatory effect on HUVECs permeability by modifying the distribution of VE cadherin. Our results confirm that melatonin blocks proangiogenic and potentiates antiangiogenic effects induced by docetaxel and vinorelbine enhancing their antitumor effectiveness.The development of new blood vessels is needed to provide oxygen and nutrients to the tumor cells and a way to escape from the primary site 1 . Angiogenesis is a main step in tumor growth and antiangiogenic agents are considered an interesting complementary strategy in cancer therapy 2 . Angiogenesis is a multi-step process: endothelial cell activation by growth factors, degradation of capillary wall by proteinases, formation of a branch point in the vessel wall, migration of endothelial cells and proliferation and reorganisation of endothelial cells to form tubules. In tumors, the interaction between endothelial cells and the microenvironment stimulates endothelial cells to proliferate, migrate and form a branching network of tubes 3 . A balance between angiogenic activating and inhibiting factors regulates the evolution of endothelial cells from a quiescent to a proangiogenic stage 2 . Among the principal proangiogenic factors are vascular endothelial growth factor (VEGF) and angiopoietins (ANG) 4,5 . Angiogenesis depends on the coordinated balance in time between the production of VEGF and angiopoietins 6 .Melatonin, produced in the pineal gland, has antitumor effects in different cancer types, especially hormone-dependent tumors 7-10 . Melatonin oncostatic actions are exerted through different mechanisms, such as: indirect effects through a down-regulation of gonadal estrogens 11 ; direct antiestrogenic actions at the tumor cell ...

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Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 99%

Section: Measurement Of 17β-hydroxysteroid Dehydrogenase Typementioning

confidence: 99%

See 1 more Smart Citation

Usefulness of melatonin as complementary to chemotherapeutic agents at different stages of the angiogenic process

González-González

González

Rueda

et al. 2020

Sci Rep

Self Cite

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“…MT is known to enhance the effects of 5-fluorouracil [37] and potentiate apoptotic effects of docetaxel [38]. However, in our experiments, MT restored the therapeutic effectiveness of AT even when mice were exposed to MT before administration of AT.…”

Section: Discussioncontrasting

confidence: 73%

Melatonin Administered before or after a Cytotoxic Drug Increases Mammary Cancer Stabilization Rates in HER2/Neu Mice

Panchenko¹,

Tyndyk²,

Maydin³

et al. 2020

Chemotherapy

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Introduction: The effects of chemotherapy are known to depend on the time of administration. Circadian rhythms are disturbed in tumors and in tumor bearers. Agents involved in controlling the circadian rhythms (chronobiotics) potentially can modify the outcomes of chemotherapeutics administered at different times of the day. Pineal hormone melatonin (MT) is a prototypic chronobiotic. Objective: The aim of the study was to investigate if MT can affect efficacy or toxicity of chemotherapy drugs administered at the extreme time points of the working day of hospital personnel. Methods: Cyclophosphamide, adriamycin, and 5-fluorouracil (CAF) and adriamycin and docetaxel (AT) cytotoxic drug combinations were administered on day 0 at 11:00 a.m. or at 5:00 p.m.

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“…Animal studies have shown that via several mechanisms such as increasing Bcl-2 gene expression versus a significant decrease in Bax gene expression [65], decrease in caspase-3 activity [59], upregulation of bcl-2 as well as reduction of bax/bcl-2 ratio [66], and relative decline in p53 expression [67], melatonin protects against IRinduced apoptosis. Inhibition of COX-2, NF-κB, iNOS, and Sirt1, as well as TGF-β activation, has also been attributed to its antiapoptotic effect [67,68].…”

Section: Antiapoptotic Effectmentioning

confidence: 99%

Clinical Applications of Melatonin in Radiotherapy: a Review

Musa

Shabeeb

Omyan

2019

SN Compr. Clin. Med.

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Radiotherapy is a treatment method for cancers using ionizing radiation (IR). Radiotherapy-induced complications to normal tissues have been major drawbacks. One of the strategies for preventing or reducing these side effects is the use of natural radioprotectors such as melatonin. Melatonin is largely secreted in the pineal glands of mammals. Studies have evaluated its radioprotective effect mostly using animal models. However, in this review, we discuss the findings of various clinical studies that utilized melatonin in radiotherapy. Online databases (PubMed, Scopus, Embase, and Google Scholar) and ClinicalTrials.gov were searched to retrieve relevant clinical studies which utilized melatonin alongside radiotherapy. The literature reviewed showed that melatonin administration prevented radiation-induced dermatitis, delayed the onset of oral mucositis, and improved treatment outcomes as well as patients' quality of life after radiotherapy. These studies reported minimal toxicities from melatonin administration. However, their results were not in agreement in terms of patient survival. The application of melatonin in radiotherapy showed potentials for improving treatment outcomes as well as preventing or ameliorating radiotherapy-induced side effects. We recommend further clinical trials for more insights especially in areas such as optimal melatonin dose and patient survival.

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Melatonin enhances the apoptotic effects and modulates the changes in gene expression induced by docetaxel in MCF‑7 human breast cancer cells

Cited by 40 publications

References 56 publications

Usefulness of melatonin as complementary to chemotherapeutic agents at different stages of the angiogenic process

Usefulness of melatonin as complementary to chemotherapeutic agents at different stages of the angiogenic process

Melatonin Administered before or after a Cytotoxic Drug Increases Mammary Cancer Stabilization Rates in HER2/Neu Mice

Clinical Applications of Melatonin in Radiotherapy: a Review

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