Melitina: o uso do principal componente da peçonha de abelha no combate de linhagens de células tumorais pulmonares
DOI:
https://doi.org/10.11606/issn.1679-9836.v101i6e-200516Palavras-chave:
Antineoplásicos, Peptídeos, NanopartículasResumo
Introdução: Melitina é um peptídeo formado por 26 aminoácidos e principal composto da peçonha produzida por abelhas do gênero Apis. Estudos pré-clínicos têm demonstrado uma capacidade antineoplásica do composto, evidenciando seu efeito sobre linhagens celulares de câncer. O câncer de pulmão é o câncer que mais mata no mundo, sendo que 90% dos casos da doença estão relacionados a um histórico tabagista. O diagnóstico tardio muitas vezes devido à falta de sintomas clínicos compromete diretamente o tratamento e o prognóstico, gerando uma baixa taxa de sobrevida. Neste sentido, a melitina surge como uma abordagem no tratamento de câncer de pulmão. Objetivo: Realizar uma revisão integrativa da literatura sobre as pesquisas publicadas nos últimos cinco anos sobre o efeito da melitina em linhagens de células tumorais pulmonares humanas. Resultados: Foram encontradas 15 publicações, 10 foram excluídas por não responderem diretamente ao objetivo proposto ou por se tratarem de artigos duplicados e cinco foram escolhidas para compor esta revisão. Discussão: Os artigos avaliados relatam o efeito anticancerígeno da melitina sobre linhagens celulares de câncer de pulmão in vitro e in vivo. Conclusão: Devido sua atividade citotóxica a melitina é uma candidata no desenvolvimento de novos tratamentos de câncer.
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Referências
Silveira FA, Melo GAR, Almeida EAB. Abelhas brasileiras: sistemática e identificação. Belo Horizonte: Fernando A. Silveira; 2002.
Witter S, Silva PN, Blochtein B, Lisboa BB, Fonseca VLI. As abelhas e a agricultura. Porto Alegre: ediPUCRS; 2014.
Oliveira-Filho AT, Oliveira LC. Biologia floral de uma população de Solanum lycocarpum St.Hil. (Solanaceae) em Lavras, MG. Rev Bras Botânica. 1988;11(2):23-32.
Pasupuleti VR, Sammugam L, Ramesh N, Gan SH. Honey, propolis, and royal jelly: a comprehensive review of their biological actions and health benefits. Oxidative Med Cel Longevity. 2017;2017:1-21. https://doi.org/10.1155/2017/1259510
Ratajczak M, Kaminska D, Matuszewska E, Hołderna-Kedzia E, Rogacki J, Matysiak J. Promising antimicrobial properties of bioactive compounds from different honeybee products. Molecules (Basel, Suíça). 2021;26(13):4007. https://doi.org/10.3390/molecules26134007
Bridi R, Atala E, Pizarro PN, Montenegro G. Honeybee pollen load: phenolic composition and antimicrobial activity and antioxidant capacity. J Natural Products. 2019;82(3):559–65. https://doi.org/10.1021/acs.jnatprod.8b00945
Ranneh Y, Akim AM, Hamid HAb, Khazaai H, Fadel A, Zakaria ZA, et al. Honey and its nutritional and anti-inflammatory value. BMC Compl Med Ther. 2021;21(1). https://doi.org/10.1186/s12906-020-03170-5
Yosri N, Abd El-Wahed AA, Ghonaim R, Khattab OM, Sabry A, Ibrahim MAA, et al. Anti-viral and immunomodulatory properties of propolis: chemical diversity, pharmacological properties, preclinical and clinical applications, and in silico potential against SARS-CoV-2. Foods (Basel, Suíça). 2021;10(8):1776. https://doi.org/10.3390/foods10081776
Magnavacca A, Sangiovanni E, Racagni G, Dell’Agli M. The antiviral and immunomodulatory activities of propolis: An update and future perspectives for respiratory diseases. Medicinal Res Rev. 2022;42(2):897–945. https://doi.org/10.1002/med.21866
Memariani H, Memariani M, Moravvej H, Shahidi-Dadras M. Melittin: a venom-derived peptide with promising anti-viral properties. Eur J Clin Microbiol Infect Dis. 2020;39(1):5–17. https://doi.org/10.1007/s10096-019-03674-0
Ishida Y, Gao R, Shah N, Bhargava P, Furune T, Kaul SC, et al. Anticancer activity in honeybee propolis: functional insights to the role of caffeic acid phenethyl ester and its complex with γ-cyclodextrin. Integrative Cancer Ther. 2018;17(3):867–73. https://doi.org/10.1177/1534735417753545
Duffy C, Sorolla A, Wang E, Golden E, Woodward E, Davern K, et al. Honeybee venom and melittin suppress growth factor receptor activation in HER2-enriched and triple-negative breast cancer. NPJ Precision Oncol. 2020;4(1). https://doi.org/10.1038/s41698-020-00129-0
Nainu F, Masyita A, Bahar MuhA, Raihan M, Prova SR, Mitra S, et al. Pharmaceutical prospects of bee products: special focus on anticancer, antibacterial, antiviral, and antiparasitic properties. Antibiotics. 2021;10(7):822. https://doi.org/10.3390/antibiotics10070822
Zhang S, Liu Y, Ye Y, Wang X-R, Lin L-T, Xiao L-Y, et al. Bee venom therapy: Potential mechanisms and therapeutic applications. Toxicon. 2018;148:64–73. https://doi.org/10.1016/j.toxicon.2018.04.012
Ruvolo-Takasusuki MCC, Souza PM de. Apitoxina: Utilização do Veneno da abelha Apis mellifera. PUBVET. 2019;13:153. http://dx.doi.org/10.31533/pubvet.v13n8a390.1-7
Aufschnaiter A, Kohler V, Khalifa S, Abd El-Wahed A, Du M, El-Seedi H, et al. Apitoxin and its components against cancer, neurodegeneration and rheumatoid arthritis: limitations and possibilities. Toxins. 2020;12(2):66. https://doi.org/10.3390/toxins12020066
Wehbe R, Frangieh J, Rima M, El Obeid D, Sabatier J-M, Fajloun Z. Bee venom: overview of main compounds and bioactivities for therapeutic interests. Molecules. 2019;24(16). https://doi.org/10.3390%2Fmolecules24162997
Abd El-Wahed AA, Khalifa SAM, Sheikh BY, Farag MA, Saeed A, Larik FA, et al. Chapter 13 - Bee venom composition: from chemistry to biological activity. In: Atta-ur-Rahman, editor. Studies in natural products chemistry. ScienceDirect. Elsevier; 2019. v.60, p.459-484 [cited 2022 Jul 14]. https://doi.org/10.1016/B978-0-444-64181-6.00013-9
Rady I, Siddiqui IA, Rady M, Mukhtar H. Melittin, a major peptide component of bee venom, and its conjugates in cancer therapy. Cancer Lett. 2017;402:16-31. https://doi.org/10.1016/j.canlet.2017.05.010
Zhu H, Chen D, Xie X, Li Y, Fan T. Melittin inhibits lung metastasis of human osteosarcoma: Evidence of wnt/β-catenin signaling pathway participation. Toxicon. 2021;198:132-42. https://doi.org/10.1016/j.toxicon.2021.04.024
Huang J-Y, Peng S-F, Chueh F-S, Chen P-Y, Huang Y-P, Huang W-W, et al. Melittin suppresses epithelial-mesenchymal transition and metastasis in human gastric cancer AGS cells via regulating Wnt/BMP associated pathway. Biosci Biotechnol Biochem. 2021;85(11):2250-62. https://doi.org/10.1093/bbb/zbab153
Jamasbi E, Lucky SS, Li W, Hossain MA, Gopalakrishnakone P, Separovic F. Effect of dimerized melittin on gastric cancer cells and antibacterial activity. Amino Acids. 2018;50(8):1101-10. https://doi.org/10.1007/s00726-018-2587-6
Moghaddam FD, Mortazavi P, Hamedi S, Nabiuni M, Roodbari NH. Apoptotic effects of melittin on 4T1 breast cancer cell line is associated with up regulation of Mfn1 and Drp1 mRNA expression. anti-cancer agents. Med Chem. 2020;20(7):790-9. https://doi.org/10.2174/1871520620666200211091451
Mir Hassani Z, Nabiuni M, Parivar K, Abdirad S, Karimzadeh L. Melittin inhibits the expression of key genes involved in tumor microenvironment formation by suppressing HIF-1α signaling in breast cancer cells. Med Oncol (Northwood, Londres, Inglaterra). 2021;38(7):77. https://doi.org/10.1007/s12032-021-01526-6
Lischer K, Sitorus S, Guslianto B, Avila F, Khayrani A, Sahlan M. Anti-breast cancer activity on MCF-7 cells of Melittin from Indonesia’s Apis cerana: an in vitro study. Asian Pacific J Cancer Prevent. 2021;22(12):3913=20. https://doi.org/10.31557/apjcp.2021.22.12.3913
Yao J, Zhang Z, Li S, Li B, Wang X. Melittin inhibits proliferation, migration and invasion of bladder cancer cells by regulating key genes based on bioinformatics and experimental assays. J Cell Mol Med. 2019;24(1):655-70. https://doi.org/10.1111/jcmm.14775
Shaw P, Kumar N, Hammerschmid D, Privat-Maldonado A, Dewilde S, Bogaerts A. Synergistic effects of melittin and plasma treatment: a promising approach for cancer therapy. Cancers. 2019;11(8):1109. https://doi.org/10.3390/cancers11081109
Lv S, Sylvestre M, Song K, Pun SH. Development of D-melittin polymeric nanoparticles for anti-cancer treatment. Biomaterials. 2021;277:121076. https://doi.org/10.1016/j.biomaterials.2021.121076
Feng J-P, Zhu R, Jiang F, Xie J, Gao C, Li M, et al. Melittin-encapsulating peptide hydrogels for enhanced delivery of impermeable anticancer peptides. Biomaterials Sci. 2020;8(16):4559-69. https://doi.org/10.1039/C9BM02080B
Rajabnejad SH, Mokhtarzadeh A, Abnous K, Taghdisi SM, Ramezani M, Razavi BM. Targeted delivery of melittin to cancer cells by AS1411 anti-nucleolin aptamer. Drug Develop Industrial Pharm. 2018;44(6):982-7. https://doi.org/10.1080/03639045.2018.1427760
Wang J-J, Lei K-F, Han F. Tumor microenvironment: recent advances in various cancer treatments. Eur Rev Med Pharmacol Sci. 2018;22(12):3855-64. https://doi.org/10.26355/eurrev_201806_15270
Nasim F, Sabath BF, Eapen GA. Lung Cancer. Med Clin North Am. 2019;103(3):463-73. https://doi.org/10.1016/j.mcna.2018.12.006
Schabath MB, Cote ML. Cancer Progress and Priorities: Lung Cancer. Cancer Epidemiol Prev Biomark. 2019;28(10):1563–79. https://doi.org/10.1158/1055-9965.epi-19-0221
Yu R, Wang M, Wang M, Han L. Melittin suppresses growth and induces apoptosis of non-small-cell lung cancer cells via down-regulation of TGF-β-mediated ERK signal pathway. Braz J Med Biol Res. 2021;54(2). https://doi.org/10.1590/1414-431X20209017
Zhang S-F, Chen Z. Melittin exerts an antitumor effect on non-small cell lung cancer cells. Mol Med Rep. 2017;16(3):3581-6. https://doi.org/10.3892/mmr.2017.6970
Gao D, Zhang J, Bai L, Li F, Dong Y, Li Q. Melittin induces NSCLC apoptosis via inhibition of miR-183. OncoTargets Ther. 2018;11:4511-23. https://doi.org/10.2147/OTT.S169806
Jeong Y-J, Park Y-Y, Park K-K, Choi YH, Kim C-H, Chang Y-C. Bee venom suppresses EGF-induced epithelial-mesenchymal transition and tumor invasion in lung cancer cells. Am J Chinese Med. 2019;47(08):1869-83. https://doi.org/10.1142/S0192415X19500952
Tipgomut C, Wongprommoon A, Takeo E, Ittiudomrak T, Puthong S, Chanchao C. Melittin Induced G1 Cell Cycle Arrest and Apoptosis in Chago-K1 Human Bronchogenic Carcinoma Cells and Inhibited the Differentiation of THP-1 Cells into Tumour- Associated Macrophages. Asian Pacific J Cancer Prev APJCP. 2018;19(12):3427-34. https://doi.org/10.31557/apjcp.2018.19.12.3427
Lee C, Bae S-JS, Joo H, Bae H. Melittin suppresses tumor progression by regulating tumor-associated macrophages in a Lewis lung carcinoma mouse model. Oncotarget. 2017;8(33):54951–65. https://doi.org/10.18632/oncotarget.18627
Su L, Xu G, Shen J, Tuo Y, Zhang X, Jia S, et al. Anticancer bioactive peptide suppresses human gastric cancer growth through modulation of apoptosis and the cell cycle. Oncology Rep. 2010;23(1):3–9. https://doi.org/10.3892/or.2017.5778
Lee YG, Kim JY, Lee KW, Kim KH, Lee HJ. Peptides from anchovy sauce induce apoptosis in a human lymphoma cell (U937) through the increase of caspase-3 and -8 activities. Ann New York Acad Sci. 2003;1010:399-404. https://doi.org/10.1196/annals.1299.073
Williams DE, Yu K, Behrisch HW, Van Soest R, Andersen RJ. Rolloamides A and B, cytotoxic cyclic heptapeptides isolated from the caribbean marine sponge Eurypon laughlini. J Natural Products. 2009;72(7):1253-7. https://doi.org/10.1021/np900121m
Kim E-K. Purification of a novel anticancer peptide from enzymatic hydrolysate of mytilus coruscus. J Microbiol Biotechnol. 2012;22(10):1381-7. https://doi.org/10.4014/jmb.1207.07015
Conlon JM, Mechkarska M, Prajeep M, Arafat K, Zaric M, Lukic ML, et al. Transformation of the naturally occurring frog skin peptide, alyteserin-2a into a potent, non-toxic anti-cancer agent. Amino Acids. 2013;44(2):715–23. https://doi.org/10.1007/s00726-012-1395-7
Skjånes K, Aesoy R, Herfindal L, Skomedal H. Bioactive peptides from microalgae: focus on anti‐cancer and immunomodulating activity. Physiol Plantarum. 2021;173(2):612-23. https://doi.org/10.1111/ppl.13472
Huang J-Y, Peng S-F, Chueh F-S, Chen P-Y, Huang Y-P, Huang W-W, et al. Melittin suppresses epithelial-mesenchymal transition and metastasis in human gastric cancer AGS cells via regulating Wnt/BMP associated pathway. Biosci Biotechnol Biochem. 2021;85(11):2250-62. https://doi.org/10.1093/bbb/zbab153
Shin J-M, Jeong Y-J, Cho H-J, Park K-K, Chung I-K, Lee I-K, et al. Melittin Suppresses HIF-1α/VEGF Expression through Inhibition of ERK and mTOR/p70S6K Pathway in Human Cervical Carcinoma Cells. Woloschak GE, editor. PLoS ONE. 2013;8(7):e69380. https://doi.org/10.1371/journal.pone.0069380
Mir Hassani Z, Nabiuni M, Parivar K, Abdirad S, Karimzadeh L. Melittin inhibits the expression of key genes involved in tumor microenvironment formation by suppressing HIF-1α signaling in breast cancer cells. Med Oncol (Northwood, London, England). 2021;38(7):77. https://doi.org/10.1007/s12032-021-01526-6
Zhou J, Wan C, Cheng J, Huang H, Lovell JF, Jin H. Delivery strategies for melittin-based cancer therapy. ACS Appl Materials Interfaces. 2021;13(15):17158-73. https://doi.org/10.1021/acsami.1c03640
Chiangjong W, Chutipongtanate S, Hongeng S. Anticancer peptide: Physicochemical property, functional aspect and trend in clinical application (Review). Int J Oncol. 2020;57(3):678-96. https://doi.org/10.3892/ijo.2020.5099
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