Melatonin as an Adjuvant to Antiangiogenic Cancer Treatments
Abstract
:Simple Summary
Abstract
1. Introduction: Melatonin, an Antitumor Hormone
2. Angiogenic Factors and Cancer
3. Melatonin Antiangiogenic Actions and Cancer
4. Melatonin Antiangiogenic Actions and Chemotherapy
5. Melatonin Antiangiogenic Actions and Radiation Therapy
5.1. Antiangiogenic Actions and Radiation Therapy
5.2. Melatonin as an Antiangiogenic Agent: Synergistic Effects with Ionizing Radiation
6. Clinical Trials with Melatonin as Sensitizer to Other Antitumor Treatments
7. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Changes in Angiogenesis related genes expression | Cytokines and angiogenic factors | ↓ Expression of CCL2 | Immunoregulatory and inflammatory processes |
↓ Expression of CXCL6 | Chemotactic and angiogenic properties | ||
↓ Expression of ERK1/2, AKT1 | Cell growth and differentiation | ||
↓ Expression of VEGFA, ANGPT2 | Angiogenesis and vascular development | ||
Growth Factors and receptors | ↓ Expression of FGFR3, IGF-1 | Breast cancer: migration and proliferation | |
↓ Expression of JAG1 | Hematopoiesis and angiogenesis | ||
↓ Expression of TGFα | Cell proliferation and differentiation | ||
↓ Expression of KDR, ANPEP | Angiogenesis and vascular development | ||
Proteases and extracellular matrix molecules | ↓ Expression of MMP14 | Cell growth, migration and tumor invasion | |
↑ Expression of TIMP1 | Degradation extracellular matrix and suppress proliferation | ||
Modulation of estrogen biosynthesis | Decrease aromatase, sulfatase and 17β-HSD1 expression and activity | ||
Inhibition of COX1/COX2 enzymes | |||
Modulation of different steps of the angiogenic process | Decrease vascular area (CAM assay) | ||
Inhibition of the activation of p-AKT and p-ERK | |||
↓ Permeability and VE-cadherin internalization | |||
Inhibition of cell proliferation, migration, and tubular network |
Tumor Type | Treatment | Melatonin Dose | Effects | Reference |
---|---|---|---|---|
Metastatic tumors | Chemotherapy | Induction 20 mg/day Then 10 mg/day | ↓ Tumor progression | [163] |
Advanced non-small cell lung cancer | Interleukin-2 | 10 mg/day starting 7 days before interleukin-2 | 50% Tumor control 20% Partial regression immunostimulatory effect | [164] |
Glioblastoma | Radiotherapy | 20 mg/day | ↑ Survival ↓ Side effects | [161] |
Non-small cell lung cancer | Cisplatin + Etoposide | 20 mg/day | ↑ Tumor regression ↑ Survival ↓ Side effects | [166] |
Non-small cell lung cancer, breast cancer, gastrointestinal tract cancer, head and neck cancers | Cisplatin + Etoposide Gemcitabine Doxorubicin Paclitaxel Mitoxantrone 5-Fluorouracil + Folinic acid 5-Fluorouracil + Cisplatin | 20 mg/day, starting 7 days before chemotherapy | ↑ Tumor regression ↑ Complete response ↑ Survival | [167] |
Advanced hepatocarcinoma | Transcatheter arterial chemoembolization | 20 mg/day starting 7 days before | ↑ Efficacy ↑ Survival Improve liver function | [168] |
Non-small cell lung cancer | Cisplatin + Etoposide | 20 mg/day starting 7 days before | ↑ Tumor regression ↑ Survival | [169] |
Advanced colorectal cancer | Irinotecan | 20 mg/day | ↑ Tumor regression | [170] |
Different types of cancer | Several chemotherapeutic agents Radiotherapy | 10 mg/day 20 mg/day 40 mg/day | ↑ Tumor response ↑ Survival ↓ Side effects | [179] |
Gastric cancer Colorectal cancerNon-small cell lung cancer | Cisplatin + Etoposide Cisplatin + Gemcitabine Oxaliplatin + Folinic acid +5-Fluorouracil Cisplatin + Etoposide+ leucovorin + 5-Fluorouracil 5-Fluorouracil + Folinic acid | 20 mg/day | ↑ Tumor response ↑ Survival ↓ Side effects | [171] |
Lung cancer | Somatostatine, Retinoids, Vitamin D, Bromocriptine, Cyclophosphamide | 20 mg/day | ↓ Side effects ↓ Respiratory and general symptoms | [172] |
Rectal cancer Cervical cancer | Pelvic radiation IL-2 | 20 mg/day | ↑ Efficacy IL-2 ↑ Lymphocyte proliferation ↓ Number CD4s | [174] |
Different types of cancer | Several chemotherapeutic agents | 20 mg/day 40 mg/day | ↑ Tumor response ↑ Survival ↓ Side effects | [180] |
Non-small cell lung cancer | Chemotherapy regimens | 10 mg/day 20 mg/day | Better assessment of health-related quality of life | [173] |
Rectal cancer | Radiotherapy | 20 mg/day | ↓ Side effects in blood | [183] |
Head and neck cancer | Radiotherapy | 20 mg/day | ↓ Mucositis ↓ Oral lesions | [182] |
Oral squamous cell carcinoma | Taxane, Cisplatin, 5-Fluorouracil | 20 mg/day | ↓ miR-210 and CD44 but not significant | [184] |
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González, A.; Alonso-González, C.; González-González, A.; Menéndez-Menéndez, J.; Cos, S.; Martínez-Campa, C. Melatonin as an Adjuvant to Antiangiogenic Cancer Treatments. Cancers 2021, 13, 3263. https://doi.org/10.3390/cancers13133263
González A, Alonso-González C, González-González A, Menéndez-Menéndez J, Cos S, Martínez-Campa C. Melatonin as an Adjuvant to Antiangiogenic Cancer Treatments. Cancers. 2021; 13(13):3263. https://doi.org/10.3390/cancers13133263
Chicago/Turabian StyleGonzález, Alicia, Carolina Alonso-González, Alicia González-González, Javier Menéndez-Menéndez, Samuel Cos, and Carlos Martínez-Campa. 2021. "Melatonin as an Adjuvant to Antiangiogenic Cancer Treatments" Cancers 13, no. 13: 3263. https://doi.org/10.3390/cancers13133263