Melatonin in cancer biology: pathways, derivatives, and the promise of targeted delivery

References

• Acuña-Castroviejo D, Escames G, Venegas C, Díaz-Casado ME, Lima-Cabello E, López LC, Rosales-Corral S, Tan D-X, Reiter RJ. 2014. Extrapineal melatonin: sources, regulation, and potential functions. Cell Mol Life Sci. 71(16):2997–3025. doi: 10.1007/s00018-014-1579-2.
   PubMed Web of Science ®Google Scholar
• Aghaz F, Asadi Z, Sajadimajd S, Kashfi K, Arkan E, Rahimi Z. 2023. Codelivery of resveratrol melatonin utilizing pH responsive sericin based nanocarriers inhibits the proliferation of breast cancer cell line at the different pH. Sci Rep. 13(1):11090. doi: 10.1038/s41598-023-37668-y.
   PubMed Web of Science ®Google Scholar
• Amaral FD, Cipolla-Neto J. 2018. A brief review about melatonin, a pineal hormone. Arch Endocrinol Metab. 62(4):472–479. doi: 10.20945/2359-3997000000066.
   PubMed Web of Science ®Google Scholar
• Baghban Rahimi S, Mohebbi A, Vakilzadeh G, Biglari P, Razeghi Jahromi S, Mohebi SR, Shirian S, Gorji A, Ghaemi A. 2018. Enhancement of therapeutic DNA vaccine potency by melatonin through inhibiting VEGF expression and induction of antitumor immunity mediated by CD8+ T cells. Arch Virol. 163(3):587–597. doi: 10.1007/s00705-017-3647-z.
   PubMed Web of Science ®Google Scholar
• Banerjee V, Sharda N, Huse J, Singh D, Sokolov D, Czinn SJ, Blanchard TG, Banerjee A. 2021. Synergistic potential of dual andrographolide and melatonin targeting of metastatic colon cancer cells: using the Chou-Talalay combination index method. Eur J Pharmacol. 897:173919. doi: 10.1016/j.ejphar.2021.173919.
   PubMed Web of Science ®Google Scholar
• Bilanges B, Posor Y, Vanhaesebroeck B. 2019. PI3K isoforms in cell signalling and vesicle trafficking. Nat Rev Mol Cell Biol. 20(9):515–534. doi: 10.1038/s41580-019-0129-z.
   PubMed Web of Science ®Google Scholar
• Bu S, Wang Q, Sun J, Li X, Gu T, Lai D. 2020. Melatonin suppresses chronic restraint stress-mediated metastasis of epithelial ovarian cancer via NE/AKT/β-catenin/SLUG axis. Cell Death Dis. 11(8):644. doi: 10.1038/s41419-020-02906-y.
   PubMed Web of Science ®Google Scholar
• Calastretti A, Gatti G, Lucini V, Dugnani S, Canti G, Scaglione F, Bevilacqua A. 2018. Melatonin analogue antiproliferative and cytotoxic effects on human prostate cancer cells. Int J Mol Sci. 19(5):1505. doi: 10.3390/ijms19051505.
   PubMed Web of Science ®Google Scholar
• Cardinali DP. 2019. Melatonin: clinical perspectives in neurodegeneration. Front Endocrinol (Lausanne). 10:480. doi: 10.3389/fendo.2019.00480.
   PubMed Web of Science ®Google Scholar
• Chao C-C, Chen P-C, Chiou P-C, Hsu C-J, Liu P-I, Yang Y-C, Reiter RJ, Yang S-F, Tang C-H. 2019. Melatonin suppresses lung cancer metastasis by inhibition of epithelial-mesenchymal transition through targeting to twist. Clin Sci (Lond). 133(5):709–722. doi: 10.1042/CS20180945.
   PubMed Web of Science ®Google Scholar
• Chen Y-T, Yang C-C, Shao P-L, Huang C-R, Yip H-K. 2019. Melatonin-mediated downregulation of ZNF746 suppresses bladder tumorigenesis mainly through inhibiting the AKT-MMP-9 signaling pathway. J Pineal Res. 66(1):e12536.
   PubMed Web of Science ®Google Scholar
• Cho JH, Bhutani S, Kim CH, Irwin MR. 2021. Anti-inflammatory effects of melatonin: a systematic review and meta-analysis of clinical trials. Brain Behav Immun. 93:245–253. doi: 10.1016/j.bbi.2021.01.034.
   PubMed Web of Science ®Google Scholar
• Cipolla-Neto J, Amaral FD. 2018. Melatonin as a hormone: new physiological and clinical insights. Endocr Rev. 39(6):990–1028. doi: 10.1210/er.2018-00084.
   PubMed Web of Science ®Google Scholar
• Cucielo MS, Freire PP, Emílio-Silva MT, Romagnoli GG, Carvalho RF, Kaneno R, Hiruma-Lima CA, Delella FK, Reiter RJ, Chuffa LdA 2023. Melatonin enhances cell death and suppresses the metastatic capacity of ovarian cancer cells by attenuating the signaling of multiple kinases. Pathol Res Pract. 248:154637. doi: 10.1016/j.prp.2023.154637.
   PubMed Web of Science ®Google Scholar
• DeMuro RL, Nafziger AN, Blask DE, Menhinick AM, Bertino JS. 2000. The absolute bioavailability of oral melatonin. J Clin Pharmacol. 40(7):781–784. doi: 10.1177/00912700022009422.
   PubMed Web of Science ®Google Scholar
• Dong Y, Cao X, Huang J, Hu Z, Chen C, Chen M, Long Q, Xu Z, Lv D, Rong Y, et al. 2023. Melatonin inhibits fibroblast cell functions and hypertrophic scar formation by enhancing autophagy through the MT2 receptor-inhibited PI3K/Akt/mTOR signaling. Biochim Biophys Acta Mol Basis Dis. 1870(1):166887. doi: 10.1016/j.bbadis.2023.166887.
   PubMed Web of Science ®Google Scholar
• Elsabagh HH, Moussa E, Mahmoud SA, Elsaka RO, Abdelrahman H. 2020. Efficacy of melatonin in prevention of radiation-induced oral mucositis: a randomized clinical trial. Oral Dis. 26(3):566–572. doi: 10.1111/odi.13265.
   PubMed Web of Science ®Google Scholar
• Emet M, Ozcan H, Ozel L, Yayla M, Halici Z, Hacimuftuoglu A. 2016. A review of melatonin, its receptors and drugs. Eurasian J Med. 48(2):135–141. doi: 10.5152/eurasianjmed.2015.0267.
   PubMedGoogle Scholar
• Erdogan CS, Al Hassadi Y, Aru B, Yılmaz B, Gemici B. 2022. Combinatorial effects of melatonin and paclitaxel differ depending on the treatment scheme in colorectal cancer in vitro. Life Sci. 308:120927. doi: 10.1016/j.lfs.2022.120927.
   PubMed Web of Science ®Google Scholar
• Fan L, Sun G, Ma T, Zhong F, Lei Y, Li X, Wei W. 2013. Melatonin reverses tunicamycin-induced endoplasmic reticulum stress in human hepatocellular carcinoma cells and improves cytotoxic response to doxorubicin by increasing CHOP and decreasing survivin. J Pineal Res. 55(2):184–194. doi: 10.1111/jpi.12061.
   PubMed Web of Science ®Google Scholar
• Fan L, Sun G, Ma T, Zhong F, Wei W. 2013. Melatonin overcomes apoptosis resistance in human hepatocellular carcinoma by targeting survivin and XIAP. J Pineal Res. 55(2):174–183. doi: 10.1111/jpi.12060.
   PubMed Web of Science ®Google Scholar
• Fang Z, Jung KH, Yan HH, Kim S-J, Rumman M, Park JH, Han B, Lee JE, Kang YW, Lim JH, et al. 2018. Melatonin synergizes with sorafenib to suppress pancreatic cancer via melatonin receptor and PDGFR-β/STAT3 pathway. Cell Physiol Biochem. 47(5):1751–1768. doi: 10.1159/000491058.
   PubMedGoogle Scholar
• Ferlazzo N, Andolina G, Cannata A, Costanzo MG, Rizzo V, Currò M, Ientile R, Caccamo D. 2020. Is melatonin the cornucopia of the 21st century? Antioxidants. 9(11):1088. doi: 10.3390/antiox9111088.
   Web of Science ®Google Scholar
• Gao Y, Xiao X, Zhang C, Yu W, Guo W, Zhang Z, Li Z, Feng X, Hao J, Zhang K, et al. 2017. Melatonin synergizes the chemotherapeutic effect of 5-fluorouracil in colon cancer by suppressing PI3K/AKT and NF-κB/iNOS signaling pathways. J Pineal Res. 62(2):e12380.
   Web of Science ®Google Scholar
• Gatti G, Lucini V, Dugnani S, Calastretti A, Spadoni G, Bedini A, Rivara S, Mor M, Canti G, Scaglione F, et al. 2017. Antiproliferative and pro-apoptotic activity of melatonin analogues on melanoma and breast cancer cells. Oncotarget. 8(40):68338–68353. doi: 10.18632/oncotarget.20124.
   PubMedGoogle Scholar
• Ghadrdan E, Sadighi S, Ebrahimpour S, Abdollahi A, Hadjibabaei M, Gholami K, Jahangard-Rafsanjani Z. 2020. The effect of melatonin on cisplatin-induced nephrotoxicity: a pilot, randomized, double-blinded, placebo-controlled clinical trial. Eur J Integr Med. 34:101065. doi: 10.1016/j.eujim.2020.101065.
   Web of Science ®Google Scholar
• González-González A, González A, Rueda N, Alonso-González C, Menéndez JM, Martínez-Campa C, Mitola S, Cos S. 2020. Usefulness of melatonin as complementary to chemotherapeutic agents at different stages of the angiogenic process. Sci Rep. 10(1):4790. doi: 10.1038/s41598-020-61622-x.
   PubMed Web of Science ®Google Scholar
• Grutsch J, Hrushesky W, Lis C, Levin R, Birdsall T, Wood P, Huff DF, Reynolds J, Pearl D, Shen X, et al. 2022. Daily evening melatonin prolongs survival among patients with advanced non-small-cell lung cancer. Biol Rhythm Res. 53(7):1043–1057. doi: 10.1080/09291016.2021.1899485.
   Web of Science ®Google Scholar
• Gu H, Shen Q, Mei D, Yang Y, Wei R, Ni M. 2020. Melatonin inhibits TE-1 esophageal cancer cells metastasis by suppressing the NF-κB signaling pathway and decreasing MMP-9. Ann Clin Lab Sci. 50(1):65–72.
   PubMed Web of Science ®Google Scholar
• Guan Q, Wang Z, Cao J, Dong Y, Chen Y. 2021. Mechanisms of melatonin in obesity: a review. Int J Mol Sci. 23(1):218. doi: 10.3390/ijms23010218.
   PubMed Web of Science ®Google Scholar
• Gurunathan S, Jeyaraj M, Kang M-H, Kim J-H. 2020. Melatonin enhances palladium-nanoparticle-induced cytotoxicity and apoptosis in human lung epithelial adenocarcinoma cells A549 and H1229. Antioxid Basel Switz. 9(4):357. doi: 10.3390/antiox9040357.
   PubMed Web of Science ®Google Scholar
• Haider M, Abdin SM, Kamal L, Orive G. 2020. Nanostructured lipid carriers for delivery of chemotherapeutics: a review. Pharmaceutics. 12(3):288. doi: 10.3390/pharmaceutics12030288.
   PubMed Web of Science ®Google Scholar
• Hao J, Fan W, Li Y, Tang R, Tian C, Yang Q, Zhu T, Diao C, Hu S, Chen M, et al. 2019. Melatonin synergizes BRAF-targeting agent vemurafenib in melanoma treatment by inhibiting iNOS/hTERT signaling and cancer-stem cell traits. J Exp Clin Cancer Res. 38(1):48. doi: 10.1186/s13046-019-1036-z.
   PubMedGoogle Scholar
• Hardeland R. 2017. Melatonin and the electron transport chain. Cell Mol Life Sci. 74(21):3883–3896. doi: 10.1007/s00018-017-2615-9.
   PubMed Web of Science ®Google Scholar
• Harpsøe NG, Andersen LPH, Gögenur I, Rosenberg J. 2015. Clinical pharmacokinetics of melatonin: a systematic review. Eur J Clin Pharmacol. 71(8):901–909. doi: 10.1007/s00228-015-1873-4.
   PubMed Web of Science ®Google Scholar
• Huang Y, Yuan K, Tang M, Yue J, Bao L, Wu S, Zhang Y, Li Y, Wang Y, Ou X, et al. 2021. Melatonin inhibiting the survival of human gastric cancer cells under ER stress involving autophagy and Ras-Raf-MAPK signalling. J Cell Mol Med. 25(3):1480–1492. doi: 10.1111/jcmm.16237.
   PubMed Web of Science ®Google Scholar
• Hwang SJ, Jung Y, Song Y-S, Park S, Park Y, Lee H-J. 2021. Enhanced anti-angiogenic activity of novel melatonin-like agents. J Pineal Res. 71(1):e12739.
   PubMed Web of Science ®Google Scholar
• Ikram M, Park HY, Ali T, Kim MO. 2021. Melatonin as a potential regulator of oxidative stress, and neuroinflammation: mechanisms and implications for the management of brain injury-induced neurodegeneration. J Inflamm Res. 14:6251–6264. doi: 10.2147/JIR.S334423.
   PubMed Web of Science ®Google Scholar
• Jafari H, Hassanpour M, Akbari A, Rezaie J, Gohari G, Mahdavinia GR, Jabbari E. 2021. Characterization of pH-sensitive chitosan/hydroxypropyl methylcellulose composite nanoparticles for delivery of melatonin in cancer therapy. Mater Lett. 282:128818. doi: 10.1016/j.matlet.2020.128818.
   Web of Science ®Google Scholar
• Johnson DE, O’Keefe RA, Grandis JR. 2018. Targeting the IL-6/JAK/STAT3 signalling axis in cancer. Nat Rev Clin Oncol. 15(4):234–248. doi: 10.1038/nrclinonc.2018.8.
   PubMed Web of Science ®Google Scholar
• Karim A, Tolbert D, Cao C. 2006. Disposition kinetics and tolerance of escalating single doses of ramelteon, a high-affinity MT1 and MT2 melatonin receptor agonist indicated for treatment of insomnia. J Clin Pharmacol. 46(2):140–148. doi: 10.1177/0091270005283461.
   PubMed Web of Science ®Google Scholar
• Kartini D, Taher A, Panigoro SS, Setiabudy R, Jusman SW, Haryana SM, Abdullah M, Rustamadji P, Purwanto DJ, Sutandyo N. 2020. Effect of melatonin supplementation in combination with neoadjuvant chemotherapy to miR-210 and CD44 expression and clinical response improvement in locally advanced oral squamous cell carcinoma: a randomized controlled trial. J Egypt Natl Cancer Inst. 32(1):12.
   PubMed Web of Science ®Google Scholar
• Kast RE. 2015. Agomelatine or ramelteon as treatment adjuncts in glioblastoma and other M1- or M2-expressing cancers. Contemp Oncol (Pozn). 19(2):157–162. doi: 10.5114/wo.2015.51421.
   PubMedGoogle Scholar
• Kouhi Habibi N, Monfared AS, Gorji KE, Karimi M, Moghadamnia AA, Tourani M, Borzoueisileh S, Niksirat F. 2019. The protective effects of melatonin on blood cell counts of rectal cancer patients following radio-chemotherapy: a randomized controlled trial. Clin Transl Oncol. 21(6):745–752. doi: 10.1007/s12094-018-1977-2.
   PubMed Web of Science ®Google Scholar
• Kumar Yadav S, Kumar Srivastava A, Dev A, Kaundal B, Roy Choudhury S, Karmakar S. 2017. Nanomelatonin triggers superior anticancer functionality in a human malignant glioblastoma cell line. Nanotechnology. 28(36):365102. doi: 10.1088/1361-6528/aa7c76.
   PubMed Web of Science ®Google Scholar
• L Y, P S, Zhao G, X J, P W, Z J, Zhang G, W X, D Z, C F, et al. 2020. Targeting cancer stem cell pathways for cancer. Signal Transduct Target Ther. 5(1):288.
   PubMed Web of Science ®Google Scholar
• Lee S, Rauch J, Kolch W. 2020. Targeting MAPK signaling in cancer: mechanisms of drug resistance and sensitivity. Int J Mol Sci. 21(3):1102. doi: 10.3390/ijms21031102.
   Web of Science ®Google Scholar
• Li M, Hao B, Zhang M, Reiter RJ, Lin S, Zheng T, Chen X, Ren Y, Yue L, Abay B, et al. 2021. Melatonin enhances radiofrequency-induced NK antitumor immunity, causing cancer metabolism reprogramming and inhibition of multiple pulmonary tumor development. Signal Transduct Target Ther. 6(1):330.
   PubMed Web of Science ®Google Scholar
• Li Y, Zou J, Li B, Du J. 2021. Anticancer effects of melatonin via regulating lncRNA JPX-Wnt/β-catenin signalling pathway in human osteosarcoma cells. J Cellular Molecular Medi. 25(20):9543–9556. doi: 10.1111/jcmm.16894.
   PubMed Web of Science ®Google Scholar
• Li Y-C, Chen C-H, Chang C-L, Chiang JY-W, Chu C-H, Chen H-H, Yip H-K. 2021. Melatonin and hyperbaric oxygen therapies suppress colorectal carcinogenesis through pleiotropic effects and multifaceted mechanisms. Int J Biol Sci. 17(14):3728–3744. doi: 10.7150/ijbs.62280.
   PubMed Web of Science ®Google Scholar
• Lin L, Li Z, Yan L, Liu Y, Yang H, Li H. 2021. Global, regional, and national cancer incidence and death for 29 cancer groups in 2019 and trends analysis of the global cancer burden, 1990-2019. J Hematol Oncol. 14(1):197. doi: 10.1186/s13045-021-01213-z.
   PubMed Web of Science ®Google Scholar
• Lin P-H, Tung Y-T, Chen H-Y, Chiang Y-F, Hong H-C, Huang K-C, Hsu S-P, Huang T-C, Hsia S-M. 2020. Melatonin activates cell death programs for the suppression of uterine leiomyoma cell proliferation. J Pineal Res. 68(1):e12620.
   PubMed Web of Science ®Google Scholar
• Lin S, Hoffmann K, Gao C, Petrulionis M, Herr I, Schemmer P. 2017. Melatonin promotes sorafenib-induced apoptosis through synergistic activation of JNK/c-jun pathway in human hepatocellular carcinoma. J Pineal Res. 62(3):e12398.
   Web of Science ®Google Scholar
• Liu Lei, Wang T, Yang X, Xu C, Liao Z, Wang X, Su D, Li Y, Zhou H, Qiu X, et al. 2019. MTNR1B loss promotes chordoma recurrence by abrogating melatonin-mediated β-catenin signaling repression. J Pineal Res. 67(2):e12588. doi: 10.1111/jpi.12588.
   Web of Science ®Google Scholar
• Liu D, Shi K, Fu M, Chen F. 2021. Melatonin indirectly decreases gastric cancer cell proliferation and invasion via effects on cancer-associated fibroblasts. Life Sci. 277:119497. doi: 10.1016/j.lfs.2021.119497.
   PubMed Web of Science ®Google Scholar
• Liu K, Song J, Yan Y, Zou K, Che Y, Wang B, Li Z, Yu W, Guo W, Zou L, et al. 2021. Melatonin increases the chemosensitivity of diffuse large B-cell lymphoma cells to epirubicin by inhibiting P-glycoprotein expression via the NF-κB pathway. Transl Oncol. 14(1):100876. doi: 10.1016/j.tranon.2020.100876.
   PubMed Web of Science ®Google Scholar
• Liu S, Liang B, Jia H, Jiao Y, Pang Z, Huang Y. 2017. Evaluation of cell death pathways initiated by antitumor drugs melatonin and valproic acid in bladder cancer cells. FEBS Open Bio. 7(6):798–810. doi: 10.1002/2211-5463.12223.
   PubMed Web of Science ®Google Scholar
• Long F, Dong C, Jiang K, Xu Y, Chi X, Sun D, Liang R, Gao Z, Shao S, Wang L. 2017. Melatonin enhances the anti-tumor effect of sorafenib via AKT/p27-mediated cell cycle arrest in hepatocarcinoma cell lines. RSC Adv. 7(34):21342–21351. doi: 10.1039/C7RA02113E.
   Web of Science ®Google Scholar
• Lozano A, Marruecos J, Rubió J, Farré N, Gómez-Millán J, Morera R, Planas I, Lanzuela M, Vázquez-Masedo MG, Cascallar L, et al. 2021. Randomized placebo-controlled phase II trial of high-dose melatonin mucoadhesive oral gel for the prevention and treatment of oral mucositis in patients with head and neck cancer undergoing radiation therapy concurrent with systemic treatment. Clin Transl Oncol. 23(9):1801–1810. doi: 10.1007/s12094-021-02586-w.
   PubMed Web of Science ®Google Scholar
• Ma S, Zhu L, Fan X, Luo T, Liu D, Liang Z, Hu X, Shi T, Tan W, Wang Z. 2021. Melatonin derivatives combat with inflammation-related cancer by targeting the main culprit STAT3. Eur J Med Chem. 211:113027. doi: 10.1016/j.ejmech.2020.113027.
   PubMed Web of Science ®Google Scholar
• Manchester LC, Coto-Montes A, Boga JA, Andersen LPH, Zhou Z, Galano A, Vriend J, Tan D-X, Reiter RJ. 2015. Melatonin: an ancient molecule that makes oxygen metabolically tolerable. J Pineal Res. 59(4):403–419. doi: 10.1111/jpi.12267.
   PubMed Web of Science ®Google Scholar
• Martín V, Herrera F, Carrera-Gonzalez P, García-Santos G, Antolín I, Rodriguez-Blanco J, Rodriguez C. 2006. Intracellular signaling pathways involved in the cell growth inhibition of glioma cells by melatonin. Cancer Res. 66(2):1081–1088. doi: 10.1158/0008-5472.CAN-05-2354.
   PubMed Web of Science ®Google Scholar
• Meyer-Déru L, David G, Auvergne R. 2022. Chitosan chemistry review for living organisms encapsulation. Carbohydr Polym. 295:119877. doi: 10.1016/j.carbpol.2022.119877.
   PubMed Web of Science ®Google Scholar
• Mi L, Kuang H. 2020. Melatonin regulates cisplatin resistance and glucose metabolism through hippo signaling in hepatocellular carcinoma cells. Cancer Manag Res. 12:1863–1874. doi: 10.2147/CMAR.S230466.
   PubMed Web of Science ®Google Scholar
• Minocha T, Das M, Rai V, Verma SS, Awasthee N, Gupta SC, Haldar C, Yadav SK. 2022. Melatonin induces apoptosis and cell cycle arrest in cervical cancer cells via inhibition of NF-κB pathway. Inflammopharmacology. 30(4):1411–1429. doi: 10.1007/s10787-022-00964-6.
   PubMed Web of Science ®Google Scholar
• Molska A, Nyman AKG, Sofias AM, Kristiansen KA, Hak S, Widerøe M. 2020. In vitro and in vivo evaluation of organic solvent-free injectable melatonin nanoformulations. Eur J Pharm Biopharm. 152:248–256. doi: 10.1016/j.ejpb.2020.05.003.
   PubMed Web of Science ®Google Scholar
• Moreno-SanJuan S, Puentes-Pardo JD, Casado J, Escudero-Feliu J, Khaldy H, Arnedo J, Carazo Á, León J. 2023. Agomelatine, a melatonin-derived drug, as a new strategy for the treatment of colorectal cancer. Antioxid Basel Switz. 12(4):926. doi: 10.3390/antiox12040926.
   PubMed Web of Science ®Google Scholar
• Mortezaee K, Najafi M, Farhood B, Ahmadi A, Potes Y, Shabeeb D, Musa AE. 2019. Modulation of apoptosis by melatonin for improving cancer treatment efficiency: an updated review. Life Sci. 228:228–241. doi: 10.1016/j.lfs.2019.05.009.
   PubMed Web of Science ®Google Scholar
• Moslehi M, Moazamiyanfar R, Dakkali MS, Rezaei S, Rastegar-Pouyani N, Jafarzadeh E, Mouludi K, Khodamoradi E, Taeb S, Najafi M. 2022. Modulation of the immune system by melatonin; implications for cancer therapy. Int Immunopharmacol. 108:108890. doi: 10.1016/j.intimp.2022.108890.
   PubMed Web of Science ®Google Scholar
• Niu G, Yousefi B, Qujeq D, Marjani A, Asadi J, Wang Z, Mir SM. 2021. Melatonin and doxorubicin co-delivered via a functionalized graphene-dendrimeric system enhances apoptosis of osteosarcoma cells. Mater Sci Eng C Mater Biol Appl. 119:111554. doi: 10.1016/j.msec.2020.111554.
   PubMed Web of Science ®Google Scholar
• Nyamsambuu A, Khan MA, Zhou X, Chen H-C. 2022. Molecular mechanism of inhibitory effects of melatonin on prostate cancer cell proliferation, migration and invasion. PLoS One. 17(1):e0261341. doi: 10.1371/journal.pone.0261341.
   PubMed Web of Science ®Google Scholar
• de Oliveira Junior ER, Nascimento TL, Salomão MA, da Silva ACG, Valadares MC, Lima EM. 2019. Increased nose-to-brain delivery of melatonin mediated by polycaprolactone nanoparticles for the treatment of glioblastoma. Pharm Res. 36(9):131. doi: 10.1007/s11095-019-2662-z.
   PubMed Web of Science ®Google Scholar
• Osanai K, Kobayashi Y, Otsu M, Izawa T, Sakai K, Iwashita M. 2017. Ramelteon, a selective MT1/MT2 receptor agonist, suppresses the proliferation and invasiveness of endometrial cancer cells. Hum Cell. 30(3):209–215. doi: 10.1007/s13577-017-0169-7.
   PubMed Web of Science ®Google Scholar
• Ozcan-Sezer S, Ince E, Akdemir A, Ceylan ÖÖ, Suzen S, Gurer-Orhan H. 2019. Aromatase inhibition by 2-methyl indole hydrazone derivatives evaluated via molecular docking and in vitro activity studies. Xenobiotica. 49(5):549–556. doi: 10.1080/00498254.2018.1482029.
   PubMed Web of Science ®Google Scholar
• Palmer ACS, Zortea M, Souza A, Santos V, Biazús JV, Torres ILS, Fregni F, Caumo W. 2020. Clinical impact of melatonin on breast cancer patients undergoing chemotherapy; effects on cognition, sleep and depressive symptoms: A randomized, double-blind, placebo-controlled trial. PLoS One. 15(4):e0231379. doi: 10.1371/journal.pone.0231379.
   PubMed Web of Science ®Google Scholar
• Palmer ACS, Souza A, Dos Santos VS, Cavalheiro JAC, Schuh F, Zucatto AE, Biazus JV, Torres ILDS, Fregni F, Caumo W. 2019. The effects of melatonin on the descending pain inhibitory system and neural plasticity markers in breast cancer patients receiving chemotherapy: randomized, double-blinded, placebo-controlled trial. Front Pharmacol. 10:1382. doi: 10.3389/fphar.2019.01382.
   PubMed Web of Science ®Google Scholar
• Parsons MJ, Tammela T, Dow LE. 2021. WNT as a driver and dependency in cancer. Cancer Discov. 11(10):2413–2429. doi: 10.1158/2159-8290.CD-21-0190.
   PubMed Web of Science ®Google Scholar
• Perdomo J, Quintana C, González I, Hernández I, Rubio S, Loro JF, Reiter RJ, Estévez F, Quintana J. 2020. Melatonin induces melanogenesis in human SK-MEL-1 melanoma cells involving glycogen synthase kinase-3 and reactive oxygen species. Int J Mol Sci. 21(14):4970. doi: 10.3390/ijms21144970.
   PubMed Web of Science ®Google Scholar
• Pflug KM, Sitcheran R. 2020. Targeting NF-κB-inducing kinase (NIK) in immunity, inflammation, and cancer. Int J Mol Sci. 21(22):8470. doi: 10.3390/ijms21228470.
   PubMed Web of Science ®Google Scholar
• Phiboonchaiyanan PP, Puthongking P, Chawjarean V, Harikarnpakdee S, Sukprasansap M, Chanvorachote P, Priprem A, Govitrapong P. 2021. Melatonin and its derivative disrupt cancer stem-like phenotypes of lung cancer cells via AKT downregulation. Clin Exp Pharmacol Physiol. 48(12):1712–1723. doi: 10.1111/1440-1681.13572.
   PubMed Web of Science ®Google Scholar
• Pinato DJ, Stebbing J. 2016. Melatonin: resetting the clock of cancer progression? Lancet Oncol. 17(1):23–24. doi: 10.1016/S1470-2045(15)00571-9.
   PubMed Web of Science ®Google Scholar
• Raju R, Abuwatfa WH, Pitt WG, Husseini GA. 2023. Liposomes for the treatment of brain cancer-a review. Pharm Basel Switz. 16(8):1056. doi: 10.3390/ph16081056.
   Google Scholar
• Reiter RJ, Sharma R, Rosales-Corral S, de Campos Zuccari DAP, de Almeida Chuffa LG. 2022. Melatonin: a mitochondrial resident with a diverse skill set. Life Sci. 301:120612. doi: 10.1016/j.lfs.2022.120612.
   PubMed Web of Science ®Google Scholar
• Sabzichi M, Samadi N, Mohammadian J, Hamishehkar H, Akbarzadeh M, Molavi O. 2016. Sustained release of melatonin: a novel approach in elevating efficacy of tamoxifen in breast cancer treatment. Colloids Surf B Biointerf. 145:64–71. doi: 10.1016/j.colsurfb.2016.04.042.
   PubMed Web of Science ®Google Scholar
• Sana S, Ghosh S, Das N, Sarkar S, Mandal AK. 2017. Vesicular melatonin efficiently downregulates sodium fluoride-induced rat hepato- and broncho-TNF-α, TGF-β expressions, and associated oxidative injury: a comparative study of liposomal and nanoencapsulated forms. Int J Nanomed. 12:4059–4071. doi: 10.2147/IJN.S124119.
   PubMed Web of Science ®Google Scholar
• Sanchez-Vega F, Mina M, Armenia J, Chatila WK, Luna A, La KC, Dimitriadoy S, Liu DL, Kantheti HS, Saghafinia S, et al. 2018. Oncogenic Signaling pathways in the cancer genome atlas. Cell. 173(2):321–337.e10. doi: 10.1016/j.cell.2018.03.035.
   PubMed Web of Science ®Google Scholar
• Sedighi Pashaki A, Mohammadian K, Afshar S, Gholami MH, Moradi A, Javadinia SA, Keshtpour Amlashi Z. 2021. A randomized, controlled, parallel-group, trial on the effects of melatonin on fatigue associated with breast cancer and its adjuvant treatments. Integr Cancer Ther. 20:1534735420988343. doi: 10.1177/1534735420988343.
   Web of Science ®Google Scholar
• Seely D, Legacy M, Auer RC, Fazekas A, Delic E, Anstee C, Angka L, Kennedy MA, Tai L-H, Zhang T, et al. 2021. Adjuvant melatonin for the prevention of recurrence and mortality following lung cancer resection (AMPLCaRe): a randomized placebo controlled clinical trial. eClinicalMedicine. 33:100763. doi: 10.1016/j.eclinm.2021.100763.
   PubMedGoogle Scholar
• Shen Y-Q, Guerra-Librero A, Fernandez-Gil BI, Florido J, Garcia-Lopez S, Martinez-Ruiz L, Mendivil-Perez M, Soto-Mercado V, Acuna-Castroviejo D, Ortega-Arellano H, et al. 2018. Combination of melatonin and rapamycin for head and neck cancer therapy: suppression of AKT/mTOR pathway activation, and activation of mitophagy and apoptosis via mitochondrial function regulation. J Pineal Res. 64(3):e12461.
   Web of Science ®Google Scholar
• Shokrzadeh M, Ghassemi-Barghi N. 2018. Melatonin loading chitosan-tripolyphosphate nanoparticles: application in attenuating etoposide-induced genotoxicity in HepG2 cells. Pharmacology. 102(1–2):74–80. doi: 10.1159/000489667.
   PubMed Web of Science ®Google Scholar
• Slominski AT, Hardeland R, Zmijewski MA, Slominski RM, Reiter RJ, Paus R. 2018. Melatonin: a cutaneous perspective on its production, metabolism, and functions. J Invest Dermatol. 138(3):490–499. doi: 10.1016/j.jid.2017.10.025.
   PubMed Web of Science ®Google Scholar
• Soerjomataram I, Bray F. 2021. Planning for tomorrow: global cancer incidence and the role of prevention 2020-2070. Nat Rev Clin Oncol. 18(10):663–672. doi: 10.1038/s41571-021-00514-z.
   PubMed Web of Science ®Google Scholar
• Sokolov D, Sharda N, Giri B, Hassan MS, Singh D, Tarasiewicz A, Lohr C, von Holzen U, Kristian T, Waddell J, et al. 2022. Melatonin and andrographolide synergize to inhibit the colospheroid phenotype by targeting Wnt/beta-catenin signaling. J Pineal Res. 73(1):e12808.
   PubMed Web of Science ®Google Scholar
• Song Y, Wang S. 2023. Melatonin synergistically enhances docetaxel induced endoplasmic reticulum stress to promote apoptosis by suppressing NF-κB activation in cervical cancer. Med Oncol. 40(8):219. doi: 10.1007/s12032-023-02087-6.
   PubMed Web of Science ®Google Scholar
• Su S-C, Yeh C-M, Lin C-W, Hsieh Y-H, Chuang C-Y, Tang C-H, Lee Y-C, Yang S-F. 2021. A novel melatonin-regulated lncRNA suppresses TPA-induced oral cancer cell motility through replenishing PRUNE2 expression. J Pineal Res. 71(3):e12760.
   PubMed Web of Science ®Google Scholar
• Sung E-S, Kim J-Y, Ahn YT, Lee I-W, Choi S-W, Jang H-B, Lee J-C, An WG. 2020. Melatonin exerts anticancer effects in human tongue squamous cell carcinoma cells by promoting autophagy. Anticancer Res. 40(11):6295–6303. doi: 10.21873/anticanres.14650.
   PubMed Web of Science ®Google Scholar
• Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, Bray F. 2021. Global Cancer Statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 71(3):209–249. doi: 10.3322/caac.21660.
   PubMed Web of Science ®Google Scholar
• Tai H-C, Wang S-W, Swain S, Lin L-W, Tsai H-C, Liu S-C, Wu H-C, Guo J-H, Liu C-L, Lai Y-W. 2022. Melatonin suppresses the metastatic potential of osteoblastic prostate cancers by inhibiting integrin α2 β1 expression. J Pineal Res. 72(3):e12793.
   PubMed Web of Science ®Google Scholar
• Talib WH, Alsayed AR, Abuawad A, Daoud S, Mahmod AI. 2021. Melatonin in cancer treatment: current knowledge and future opportunities. Mol Basel Switz. 26(9):2506. doi: 10.3390/molecules26092506.
   Google Scholar
• Tang H, Shi X, Zhu P, Guo W, Li J, Yan B, Zhang S. 2021. Melatonin inhibits gallbladder cancer cell migration and invasion via ERK-mediated induction of epithelial-to-mesenchymal transition. Oncol Lett. 22(2):609. doi: 10.3892/ol.2021.12870.
   PubMed Web of Science ®Google Scholar
• Tang Y-L, Sun X, Huang L-B, Liu X-J, Qin G, Wang L-N, Zhang X-L, Ke Z-Y, Luo J-S, Liang C, et al. 2019. Melatonin inhibits MLL-rearranged leukemia via RBFOX3/hTERT and NF-κB/COX-2 signaling pathways. Cancer Lett. 443:167–178. doi: 10.1016/j.canlet.2018.11.037.
   PubMed Web of Science ®Google Scholar
• Tian Q-X, Zhang Z-H, Ye Q-L, Xu S, Hong Q, Xing W-Y, Chen L, Yu D-X, Xu D-X, Xie D-D. 2021. Melatonin inhibits migration and invasion in LPS-stimulated and -unstimulated prostate cancer cells through blocking multiple EMT-relative pathways. J Inflamm Res. 14:2253–2265. doi: 10.2147/JIR.S305450.
   PubMed Web of Science ®Google Scholar
• Touitou Y, Reinberg A, Touitou D. 2017. Association between light at night, melatonin secretion, sleep deprivation, and the internal clock: health impacts and mechanisms of circadian disruption. Life Sci. 173:94–106. doi: 10.1016/j.lfs.2017.02.008.
   PubMed Web of Science ®Google Scholar
• Wagner EF, Nebreda AR. 2009. Signal integration by JNK and p38 MAPK pathways in cancer development. Nat Rev Cancer. 9(8):537–549. doi: 10.1038/nrc2694.
   PubMed Web of Science ®Google Scholar
• Wang C, Zhao Z, Qi Q, Wang J, Kong Y, Feng Z, Chen A, Li W, Zhang Q, Wang J, et al. 2021. miR-6858 plays a key role in the process of melatonin inhibition of the malignant biological behavior of glioma. J Clin Neurosci. 87:137–146. doi: 10.1016/j.jocn.2021.02.015.
   PubMed Web of Science ®Google Scholar
• Wang J, Xiao X, Zhang Y, Shi D, Chen W, Fu L, Liu L, Xie F, Kang T, Huang W, et al. 2012. Simultaneous modulation of COX-2, p300, Akt, and Apaf-1 signaling by melatonin to inhibit proliferation and induce apoptosis in breast cancer cells. J Pineal Res. 53(1):77–90. doi: 10.1111/j.1600-079X.2012.00973.x.
   PubMed Web of Science ®Google Scholar
• Wang X, Wang B, Xie J, Hou D, Zhang H, Huang H. 2018. Melatonin inhibits epithelial‑to‑mesenchymal transition in gastric cancer cells via attenuation of IL‑1β/NF‑κB/MMP2/MMP9 signaling. Int J Mol Med. 42(4):2221–2228. doi: 10.3892/ijmm.2018.3788.
   PubMed Web of Science ®Google Scholar
• Wang X, Wang B, Zhan W, Kang L, Zhang S, Chen C, Hou D, You R, Huang H. 2019. Melatonin inhibits lung metastasis of gastric cancer in vivo. Biomed Pharmacother. 117:109018. doi: 10.1016/j.biopha.2019.109018.
   PubMed Web of Science ®Google Scholar
• Wang Y, Wang P, Zheng X, Du X. 2018. Therapeutic strategies of melatonin in cancer patients: a systematic review and meta-analysis. Onco Targets Ther. 11:7895–7908. doi: 10.2147/OTT.S174100.
   PubMed Web of Science ®Google Scholar
• Wyska E. 2019. Pharmacokinetic considerations for current state-of-the-art antidepressants. Expert Opin Drug Metab Toxicol. 15(10):831–847. doi: 10.1080/17425255.2019.1669560.
   PubMed Web of Science ®Google Scholar
• Xie W, Gao Q, Wang D, Wang W, Yuan J, Guo Z, Yan H, Wang X, Sun X, Zhao L. 2017. Melatonin potentiates “inside-out” nano-thermotherapy in human breast cancer cells: a potential cancer target multimodality treatment based on melatonin-loaded nanocomposite particles. Int J Nanomed. 12:7351–7363. doi: 10.2147/IJN.S148520.
   PubMed Web of Science ®Google Scholar
• Yang C-C, Chuang F-C, Chang C-L, Huang C-R, Chen H-H, Yip H-K, Chen Y-T. 2023. Melatonin-assisted cisplatin suppresses urinary bladder cancer cell proliferation and growth through inhibiting PrPC-regulated cell stress and cell proliferation signaling. Int J Mol Sci. 24(4):3353. doi: 10.3390/ijms24043353.
   PubMed Web of Science ®Google Scholar
• Yang Y, Zhou R, Park S-Y, Back K, Bae WK, Kim KK, Kim H. 2017. 2-Hydroxymelatonin, a predominant hydroxylated melatonin metabolite in plants, shows antitumor activity against human colorectal cancer cells. Mol Basel Switz. 22(3):453. doi: 10.3390/molecules22030453.
   Google Scholar
• Yang Y-C, Chiou P-C, Chen P-C, Liu P-Y, Huang W-C, Chao C-C, Tang C-H. 2019. Melatonin reduces lung cancer stemness through inhibiting of PLC, ERK, p38, β-catenin, and twist pathways. Environ Toxicol. 34(2):203–209. doi: 10.1002/tox.22674.
   PubMed Web of Science ®Google Scholar
• Yen Y-W, Lee Y-L, Yu L-Y, Li C-E, Shueng P-W, Chiu H-C, Lo C-L. 2023. Fucoidan/chitosan layered PLGA nanoparticles with melatonin loading for inducing intestinal absorption and addressing triple-negative breast cancer progression. Int J Biol Macromol. 250:126211. doi: 10.1016/j.ijbiomac.2023.126211.
   PubMed Web of Science ®Google Scholar
• Yong W, Ma H, Na M, Gao T, Zhang Y, Hao L, Yu H, Yang H, Deng X. 2021. Roles of melatonin in the field of reproductive medicine. Biomed Pharmacother. 144:112001. doi: 10.1016/j.biopha.2021.112001.
   PubMed Web of Science ®Google Scholar
• Yu H, Lin L, Zhang Z, Zhang H, Hu H. 2020. Targeting NF-κB pathway for the therapy of diseases: mechanism and clinical study. Signal Transduct Target Ther. 5(1):209.
   PubMed Web of Science ®Google Scholar
• Yu Z, Tian X, Peng Y, Sun Z, Wang C, Tang N, Li B, Jian Y, Wang W, Huo X, et al. 2018. Mitochondrial cytochrome P450 (CYP) 1B1 is responsible for melatonin-induced apoptosis in neural cancer cells. J Pineal Res. 65(1):e12478.
   PubMed Web of Science ®Google Scholar
• Zakki SA, Muhammad JS, Li J-L, Sun L, Li M-L, Feng Q-W, Li Y-L, Cui Z-G, Inadera H. 2020. Melatonin triggers the anticancer potential of phenylarsine oxide via induction of apoptosis through ROS generation and JNK activation. Metallomics. 12(3):396–407. doi: 10.1039/c9mt00238c.
   PubMed Web of Science ®Google Scholar
• Zhang J, Xie T, Zhong X, Jiang H-L, Li R, Wang B-Y, Huang X-T, Cen B-H, Yuan Y-W. 2020. Melatonin reverses nasopharyngeal carcinoma cisplatin chemoresistance by inhibiting the Wnt/β-catenin signaling pathway. Aging (Albany NY). 12(6):5423–5438. doi: 10.18632/aging.102968.
   PubMedGoogle Scholar
• Zhang Q, Ou C, Ye S, Song X, Luo S. 2017. Construction of nanoscale liposomes loaded with melatonin via supercritical fluid technology. J Microencapsul. 34(7):687–698. doi: 10.1080/02652048.2017.1376001.
   PubMed Web of Science ®Google Scholar
• Zhao D, Yu Y, Shen Y, Liu Q, Zhao Z, Sharma R, Reiter RJ. 2019. Melatonin synthesis and function: evolutionary history in animals and plants. Front Endocrinol (Lausanne). 10:249. [Internet]. [accessed 2023 Sep 7] 10. doi: 10.3389/fendo.2019.00249.
   PubMed Web of Science ®Google Scholar
• Zharinov GM, Bogomolov OA, Chepurnaya IV, Neklasova NY, Anisimov VN. 2020. Melatonin increases overall survival of prostate cancer patients with poor prognosis after combined hormone radiation treatment. Oncotarget. 11(41):3723–3729. doi: 10.18632/oncotarget.27757.
   PubMedGoogle Scholar
• Zisapel N. 2018. New perspectives on the role of melatonin in human sleep, circadian rhythms and their regulation. Br J Pharmacol. 175(16):3190–3199. doi: 10.1111/bph.14116.
   PubMed Web of Science ®Google Scholar
• Zou Z-W, Liu T, Li Y, Chen P, Peng X, Ma C, Zhang W-J, Li P-D. 2018. Melatonin suppresses thyroid cancer growth and overcomes radioresistance via inhibition of p65 phosphorylation and induction of ROS. Redox Biol. 16:226–236. doi: 10.1016/j.redox.2018.02.025.
   PubMed Web of Science ®Google Scholar