The emergence of melatonin in oncology: Focus on colorectal cancer

Gil‐Martín, Emilio; Egea, Javier; Reíter, Russel J.; Romero, Alejandro

doi:10.1002/med.21582

Cited by 51 publications

(33 citation statements)

References 360 publications

(732 reference statements)

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“…The beneficial role of melatonin for the management of many cancers has been widely proposed [ 2 , 318 , 319 ]. However, the potential benefits of melatonin in the treatment of gastric and pancreatic carcinomas are less well known and it is, therefore, crucial to concentrate research in this area.…”

Section: Melatonin In Clinical Trialsmentioning

confidence: 99%

Melatonin in Cancer Treatment: Current Knowledge and Future Opportunities

et al. 2021

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Melatonin is a pleotropic molecule with numerous biological activities. Epidemiological and experimental studies have documented that melatonin could inhibit different types of cancer in vitro and in vivo. Results showed the involvement of melatonin in different anticancer mechanisms including apoptosis induction, cell proliferation inhibition, reduction in tumor growth and metastases, reduction in the side effects associated with chemotherapy and radiotherapy, decreasing drug resistance in cancer therapy, and augmentation of the therapeutic effects of conventional anticancer therapies. Clinical trials revealed that melatonin is an effective adjuvant drug to all conventional therapies. This review summarized melatonin biosynthesis, availability from natural sources, metabolism, bioavailability, anticancer mechanisms of melatonin, its use in clinical trials, and pharmaceutical formulation. Studies discussed in this review will provide a solid foundation for researchers and physicians to design and develop new therapies to treat and prevent cancer using melatonin.

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Section: Melatonin In Clinical Trialsmentioning

confidence: 99%

Melatonin in Cancer Treatment: Current Knowledge and Future Opportunities

et al. 2021

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“…The beneficial role of melatonin for the management of many cancers has been widely proposed [36,37,38]. However, the potential benefits of melatonin in the treatment of oral carcinomas are less well known and it is therefore, imperative to concentrate research in this area.…”

Section: The Role Of Melatonin In the Oral Cavity: Functionality Amentioning

confidence: 99%

Potential of Melatonin as Adjuvant Therapy of Oral Cancer in the Era of Epigenomics

Capote-Moreno

Ramos

Egea

et al. 2019

Cancers

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The wide variety of epigenetic controls available is rapidly expanding the knowledge of molecular biology even overflowing it. At the same time, it can illuminate unsuspected ways of understanding the etiology of cancer. New emerging therapeutic horizons, then, promise to overcome the current antitumor strategies need. The translational utility of this complexity is particularly welcome in oral cancer (OC), in which natural history is alarmingly disappointing due to the invasive and mutilating surgery, the high relapsing rate, the poor quality of life and the reduced survival after diagnosis. Melatonin activates protective receptor-dependent and receptor-independent processes that prevent tissue cancerisation and inhibit progressive tumor malignancy and metastasis. Related evidence has shown that melatonin pleiotropy encompasses gene expression regulation through all the three best-characterized epigenetic mechanisms: DNA methylation, chromatin modification, and non-coding RNA. OC has received less attention than other cancers despite prognosis is usually negative and there are no significant therapy improvements recorded in the past decade. However, a large research effort is being carried out to elucidate how melatonin´s machinery can prevent epigenetic insults that lead to cancer. In the light of recent findings, a comprehensive examination of biochemistry through which melatonin may reverse epigenetic aberrations in OC is an extraordinary opportunity to take a step forward in the clinical management of patients.

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“… 12 - 14 In addition, extensive experimental data demonstrates that this chronobiotic agent exerts oncostatic effects throughout all stages of tumor growth, from initial cell transformation to mitigation of malignant progression and metastasis; additionally, MLT alleviates the side effects and improves the welfare of radio/chemotherapy-treated patients. 15 Moreover, it inhibits CRC proliferation by increasing ROS and inducing apoptosis, autophagy, and senescence. 16 In addition, MLT also causes drug-resistant CRC cell death and inhibits CRC-colospheroids when it is co-administered with 5-FU.…”

Section: Introductionmentioning

confidence: 99%

Impact of Andrographolide and Melatonin Combinatorial Drug Therapy on Metastatic Colon Cancer Cells and Organoids

Sharda

Ikuse

Hill

et al. 2021

Clin Med Insights Oncol

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Background: The death rate (the number of deaths per 100 000 people per year) of colorectal cancer (CRC) has been dropping since 1980 due to increased screening, lifestyle-related risk factors, and improved treatment options; however, CRC is the third leading cause of cancer-related deaths in men and women in the United States. Therefore, successful therapy for CRC is an unmet clinical need. This study aimed to investigate the impacts of andrographolide (AGP) and melatonin (MLT) on CRC and the underlying mechanism. Methods: To investigate AGP and MLT anticancer effects, a series of metastatic colon cancer cell lines (T84, Colo 205, HT-29, and DLD-1) were selected. In addition, a metastatic patient-derived organoid model (PDOD) was used to monitor the anticancer effects of AGP and MLT. A series of bioassays including 3D organoid cell culture, MTT, colony formation, western blotting, immunofluorescence, and quantitative polymerase chain reaction (qPCR) were performed. Results: The dual therapy significantly promotes CRC cell death, as compared with the normal cells. It also limits CRC colony formation and disrupts the PDOD membrane integrity along with decreased Ki-67 expression. A significantly higher cleaved caspase-3 and the endoplasmic reticulum (ER) stress proteins, IRE-1 and ATF-6 expression, by 48 hours were found. This combinatorial treatment increased reactive oxygen species (ROS) levels. Apoptosis signaling molecules BAX, XBP-1, and CHOP were significantly increased as determined by qPCR. Conclusions: These findings indicated that AGP and MLT associated ER stress-mediated apoptotic metastatic colorectal cancer (mCRC) cell death through the IRE-1/XBP-1/CHOP signaling pathway. This novel combination could be a potential therapeutic strategy for mCRC cells.

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The emergence of melatonin in oncology: Focus on colorectal cancer

Cited by 51 publications

References 360 publications

Melatonin in Cancer Treatment: Current Knowledge and Future Opportunities

Melatonin in Cancer Treatment: Current Knowledge and Future Opportunities

Potential of Melatonin as Adjuvant Therapy of Oral Cancer in the Era of Epigenomics

Impact of Andrographolide and Melatonin Combinatorial Drug Therapy on Metastatic Colon Cancer Cells and Organoids

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