Lignins as potential antitumor agents: A brief review

Lisandra da Silva Lima , Ila Maranhão de Oliveira , Diego Santa Clara Marques , Maria do Carmo Alves de Lima and Iranildo José da Cruz Filho

Abstract
Cancer is the second leading cause of death worldwide, with high incidence and mortality rates. Despite the variety of treatment approaches, conventional cytotoxic chemotherapy remains the primary therapeutic option for most cancer types. Although this approach offers benefits, its high toxicity negatively affects patients' quality of life. Additional limitations include the rapid clearance of drugs from circulation and their low concentration in tumors. Moreover, multidrug resistance poses a major challenge, being the main reason for treatment failure and promoting the development of metastases. In this context, lignins emerge as a promising alternative. The literature highlights the in vitro antitumor potential of various lignins, linking this activity to the phenolic nature of these macromolecules. This brief review aimed to compare the antitumor activity of lignins in different mammalian neoplastic cells. The studies reviewed in the literature show that lignins generally exhibit promising antitumor activity. These findings emphasize that such macromolecules could be utilized as raw materials by the pharmaceutical industry.

Keywords
Lignin; Phenolic compounds; Antineoplastic agents.

Resumo
Ligninas como potenciais agentes antitumorais: breve revisão. O câncer é a segunda principal causa de morte no mundo, com altas taxas de incidência e mortalidade. Apesar da variedade de abordagens de tratamento, a quimioterapia citotóxica convencional continua sendo a principal opção terapêutica para a maioria dos tipos de câncer. Embora essa abordagem ofereça benefícios, sua alta toxicidade afeta negativamente a qualidade de vida dos pacientes. Limitações adicionais incluem a rápida eliminação de medicamentos da circulação e sua baixa concentração em tumores. Além disso, a resistência a múltiplos medicamentos representa um grande desafio, sendo a principal razão para o fracasso do tratamento e promovendo o desenvolvimento de metástases. Nesse contexto, as ligninas surgem como uma alternativa promissora. A literatura destaca o potencial antitumoral in vitro de várias ligninas, vinculando essa atividade à natureza fenólica dessas macromoléculas. Esta breve revisão teve como objetivo comparar a atividade antitumoral de ligninas em diferentes células neoplásicas de mamíferos. Os estudos revisados na literatura mostram que as ligninas geralmente exibem atividade antitumoral promissora. Essas descobertas enfatizam que tais macromoléculas podem ser utilizadas como matérias-primas pela indústria farmacêutica.

Palavras-chave
Lignina; Compostos fenólicos; Agentes antineoplásicos.

DOI
10.21438/rbgas(2024)112927


Texto completo

 Baixar este arquivo PDF

 


Referências
Almeida, H. A.; Cappellaro, A. P.; Alencar, C. G. Q.; Valério, I. J. A.; Viana, M. L. C.; Fagundes, M. F.; Silva Júnior, D. R. Epidemiologia da mortalidade de câncer de mama maligno em ambiente hospitalar no Brasil em 2021. Revista Foco, v. 16, n. 6, e2359, 2023. https://doi.org/10.54751/revistafoco.v16n6-128

Araújo, D. M. F.; Cruz Filho, I. J.; Santos, T.; Pereira, D. T. M.; Marques, D. S. C.; Lima, A. C. A.; Aquino, T. M.; Rocha, G. J. M.; Lima, M. C. A.; Nogueira, F. Biological activities and physicochemical characterization of alkaline lignins obtained from branches and leaves of Buchenavia viridiflora with potential pharmaceutical and biomedical applications. International Journal of Biological Macromolecules, v. 219, p. 224-245, 2022. https://doi.org/10.1016/j.ijbiomac.2022.07.225

Barchi, L. C.; Ramos, M. F. K. P.; Dias, A. R.; Forones, N. N.; Carvalho, M. P.; Castro, O. A. P.; Kassab, P.; Costa-Júnior, W. L.; Weston, A. C.; Zilberstein, B. Brazilian gastric cancer association guidelines (Part 2): Update on treatment. ABCD - Arquivos Brasileiros de Cirurgia Digestiva, v. 34, e1563, 2021. https://doi.org/10.1590/0102-672020210001e1563

Brabec, V.; Kasparkova, J. Molecular aspects of resistance to antitumor platinum drugs. Drug Resistance Updates, v. 5, n. 3/4, p. 147-161, 2002. https://doi.org/10.1016/S1368-7646(02)00047-X

Brandão, H. N.; David, J. P.; Couto, R. D.; Nascimento, J. A. P.; David, J. M. Química e farmacologia de quimioterápicos antineoplásicos derivados de plantas. Química Nova, v. 33, p. 1359-1369, 2010. https://doi.org/10.1590/S0100-40422010000600026

Bray, F.; Laversanne, M.; Sung, H.; Ferlay, J.; Siegel, R. L.; Soerjomataram, I.; Jemal, A. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: A Cancer Journal for Clinicians, v. 74, n. 3, p. 229-263, 2024. https://doi.org/10.3322/caac.21834

Bukowski, K.; Kciuk, M.; Kontek, R. Mechanisms of multidrug resistance in cancer chemotherapy. International Journal of Molecular Sciences, v. 21, n. 9, 3233, 2020. https://doi.org/10.3390/ijms21093233

Cong, Y.; Devoogdt, N.; Lambin, P.; Dubois, L. J.; Yaromina, A. Promising diagnostic and therapeutic approaches based on VHHs for cancer management. Cancers, v. 16, n. 2, 371, 2024. https://doi.org/10.3390/cancers16020371

Costa, M. M. Atualização em câncer de mama. Medicina, Ciência e Arte, v. 1, n. 4, p. 55-73, 2022.

Cruz, I. L.; Siqueira, P. F. O. M.; Cantuaria, L. R. M. P.; Câmara, A. C. B.; Branquinho, R. C.; Lira, T. M. T.; Pedrão, E. H.; Fernandes, C. R. Câncer de mama em mulheres no Brasil: epidemiologia, fisiopatologia, diagnóstico e tratamento - uma revisão narrativa. Brazilian Journal of Development, v. 9, n. 2, p. 7579-7589, 2023. https://doi.org/10.34117/bjdv9n2-096

Cruz Filho, I. J.; Reis, D. P.; Nascimento, P. H. B.; Marques, D. S. C.; Lima, M. C. A. Alkaline lignins from Morinda citrifolia leaves are potential immunomodulatory, antitumor, and antimicrobial agents. Anais da Academia Brasileira de Ciências, v. 95, suppl. 2, e20221026, 2023. https://doi.org/10.1590/0001-3765202320221026

Dantas, J. V. S.; Silva, L. M. M.; Alves, I. D. O. L. O impacto do câncer em adolescentes: a atuação do enfermeiro no alívio da dor. Revista Científica Mais Pontal, v. 3, n. 1, p. 110-123, 2024.

Davodabadi, F.; Sajjadi, S. F.; Sarhadi, M.; Mirghasemi, S.; Hezaveh, M. N.; Khosravi, S.; Andani, M. K.; Cordani, M.; Basiri, M.; Ghavami, S. Cancer chemotherapy resistance: Mechanisms and recent breakthrough in targeted drug delivery. European Journal of Pharmacology, v. 958, 176013, 2023. https://doi.org/10.1016/j.ejphar.2023.176013

Figueiredo, P.; Lepland, A.; Scodeller, P.; Fontana, F.; Torrieri, G.; Tiboni, M.; Shahbazi, M.-A.; Casettari, L.; Kostiainen, M. A.; Hirvonen, J.; Teesalu, T.; Santos, H. A. Peptide-guided resiquimod-loaded lignin nanoparticles convert tumor-associated macrophages from M2 to M1 phenotype for enhanced chemotherapy. Acta Biomaterialia, v. 133, p. 231-243, 2021. https://doi.org/10.1016/j.actbio.2020.09.038

Fedoros, E. I.; Tyndyk, M. L.; Popovich, I. G.; Anikin, I. V.; Yurova, M. N.; Gubareva, E. A.; Pigarev, S. E.; Panchenko, A. V.; Solovyev, N. D.; Anisimov, V. N. Assessment of antitumor activity of BP-C1, a platinum-based anticancer agent with a lignin-derived polymeric ligand, in autochthonous induced and spontaneous carcinogenesis rodent models. Journal of Trace Elements in Medicine and Biology, v. 73, 127013, 2022. https://doi.org/10.1016/j.jtemb.2022.127013

Freitas, M. C. A.; Dutra, V. A.; Graça, I. V. O.; Batalha, G. Epidemiologia do câncer de colo de útero no norte do Brasil entre 2011 e 2021: um estudo ecológico. Brazilian Journal of Health Review, v. 7, n. 4, e72306, 2024. https://doi.org/10.34119/bjhrv7n4-434

Gaspar, R.; Fardim, P. Lignin-based materials for emerging advanced applications. Current Opinion in Green and Sustainable Chemistry, v. 41, 100834, 2023. https://doi.org/10.1016/j.cogsc.2023.100834

Gielecińska, A.; Kciuk, M.; Mujwar, S.; Celik, I.; Kołat, D.; Kałuzińska-Kołat, Ż.; Kontek, R. Substances of natural origin in medicine: Plants vs. cancer. Cells, v. 12, n. 7, 986, 2023. https://doi.org/10.3390/cells12070986

Gil-Chávez, G. J.; Padhi, S. S. P.; Pereira, C. V.; Guerreiro, J. N.; Matias, A. A.; Smirnova, I. Cytotoxicity and biological capacity of sulfur-free lignins obtained in novel biorefining process. International Journal of Biological Macromolecules, v. 136, p. 697-703, 2019. https://doi.org/10.1016/j.ijbiomac.2019.06.021

Gordobil, O.; Oberemko, A.; Saulis, G.; Baublys, V.; Labidi, J. In vitro cytotoxicity studies of industrial Eucalyptus Kraft lignins on mouse hepatoma, melanoma and Chinese hamster ovary cells. International Journal of Biological Macromolecules, v. 135, p. 353-361, 2019. https://doi.org/10.1016/j.ijbiomac.2019.05.111

Hu, M.; Lv, X.; Wang, Y.; Ma, L.; Zhang, Y.; Dai, H. Recent advance on lignin-containing nanocelluloses: The key role of lignin. Carbohydrate Polymers, v. 343, 122460, 2024. https://doi.org/10.1016/j.carbpol.2024.122460

INCA - Instituto Nacional de Câncer José Alencar Gomes da Silva. O que é câncer? 2022. Available from: <https://www.gov.br/inca/pt-br/assuntos/cancer/o-que-e-cancer>. Accessed on: Oct. 01, 2024.

Jia, Y.; Wu, Q.; Yang, Z.; Sun, R.; Zhang, K.; Guo, X.; Xu, R.; Guo, Y. Mechanisms of myocardial toxicity of antitumor drugs and potential therapeutic strategies: A review of the literature. Current Problems in Cardiology, v. 49, n. 11, 102782, 2024. https://doi.org/10.1016/j.cpcardiol.2024.102782

Junqueira, L. C. U.; Santos, M. A. Going through the storm: Body image and sexuality of women after breast cancer. Revista Família, Ciclos de Vida e Saúde no Contexto Social, v. 8, p. 562-574, 2020. https://doi.org/10.18554/refacs.v8i0.4669

Kumar, V.; Abbas, A. K.; Fausto, N. (Eds.). Robbins & Cotran - Patologia. São Paulo: Elsevier Brasil, 2005.

Langeh, U.; Kumar, V.; Ahuja, P.; Singh, C.; Singh, A. An update on breast cancer chemotherapy-associated toxicity and their management approaches. Health Sciences Review, v. 9, 100119, 2023. https://doi.org/10.1016/j.hsr.2023.100119

Liaqat, S.; Fatima, B.; Hussain, D.; Imran, M.; Zahra Jawad, S. E.; Imran, M.; Saeed, A.; Majeed, S. Najam-ul-Haq, M. Doxorubicin encapsulated blend of sitagliptin-lignin polymeric drug delivery system for effective combination therapy against cancer. International Journal of Biological Macromolecules, v. 269, 132146, 2024. https://doi.org/10.1016/j.ijbiomac.2024.132146

Lima, J. S.; Santos, M. L. S.; Santos, D. G. Qualidade de vida em pacientes adultos com câncer. Revista Ibero-Americana de Humanidades, Ciências e Educação, v. 10, n. 3, p. 2360-2378, 2024. https://doi.org/10.51891/rease.v10i3.13175

Lima, M. A. N.; Villela, D. A. M. Demanda e ocupação de leitos do Sistema Único de Saúde para os principais tipos de câncer no Brasil, de 2018 a 2021: estudo transversal. Epidemiologia e Serviços de Saúde, v. 33, e20231172, 2024. https://doi.org/10.1590/S2237-96222024v33e20231172.pt

Liu, S.; Xiao, S.; Wang, B.; Cai, Y.; Xie, R.; Wang, X.; Wang, J. Fractional extraction of lignin from coffee beans with low cytotoxicity, excellent anticancer and antioxidant activities. International Journal of Biological Macromolecules, v. 263, Part 2, 130509, 2024. https://doi.org/10.1016/j.ijbiomac.2024.130509

Liu, Z.; Jing, C.; Kong, F. From clinical management to personalized medicine: Novel therapeutic approaches for ovarian clear cell cancer. Journal of Ovarian Research, v. 17, n. 1, Article number: 39, 2024. https://doi.org/10.1186/s13048-024-01359-7

Lourençon, T. V.; Lima, G. G.; Ribeiro, C. S. P.; Hansel, F. A.; Maciel, G. M.; Silva, K.; Winnischofer, S. M. B.; Muniz, G. I. B.; Magalhães, W. L. E. Antioxidant, antibacterial and antitumoural activities of Kraft lignin from hardwood fractionated by acid precipitation. International Journal of Biological Macromolecules, v. 166, p. 1535-1542, 2021. https://doi.org/10.1016/j.ijbiomac.2020.11.033

Mao, X.; Wu, S.; Huang, D.; Li, C. Complications and comorbidities associated with antineoplastic chemotherapy: Rethinking drug design and delivery for anticancer therapy. Acta Pharmaceutica Sinica B, v. 14, n. 7, p. 2901-2926, 2024. https://doi.org/10.1016/j.apsb.2024.03.006

Mendes, E. C.; Vasconcellos, L. C. F. Cuidados paliativos no câncer e os princípios doutrinários do SUS. Saúde em Debate, v. 39, p. 881-892, 2015. https://doi.org/10.1590/0103-1104201510600030026

Monteiro, M. B. O.; Pereira, R. P. W.; Abreu, H. S. Bioquímica da lignificação de células xilemáticas. Floresta e Ambiente, v. 11, n. 2, p. 48-57, 2004.

Naeem, A.; Hu, P.; Yang, M.; Zhang, J.; Liu, Y.; Zhu, W.; Zheng, Q. Natural products as anticancer agents: Current status and future perspectives. Molecules, v. 27, n. 23, 8367, 2022. https://doi.org/10.3390/molecules27238367

NCI - National Cancer Institute. Understanding cancer statistics. NCI, 2023. Available from: <https://www.cancer.gov/about-cancer/understanding/statistics>. Accessed on: Oct. 14, 2024.

Nejabat, M.; Hadizadeh, F.; Sahebkar, A. The application of kinesin inhibitors in medical issues. Current Reviews in Clinical and Experimental Pharmacology, v. 19, n. 4, p. 370-378, 2024. https://doi.org/10.2174/0127724328277623231204064614

Pandit, S.; Sharma, P.; Prakash, A.; Lal, B.; Bhuyan, R.; Ahmad, I.; Kuila, A. A comprehensive review on technical lignin, lignin hydrogels, properties, preparation, applications & challenges in lab to market transition. Industrial Crops and Products, v. 211, 118262, 2024. https://doi.org/10.1016/j.indcrop.2024.118262

Santos, M. B.; Cavalcanti, M. A. T.; Medeiros e Silva, Y. M. S.; Nascimento, I. J. S.; Moura, R. O. Overview of the new bioactive heterocycles as targeting topoisomerase inhibitors useful against colon cancer. Anti-Cancer Agents in Medicinal Chemistry, v. 24, n. 4, p. 236-262, 2024. https://doi.org/10.2174/0118715206269722231121173311

Silva, B. R. M. G.; Arruda, P. O. F.; Santos, J. C. B.; Neves, R. P.; Pereira, V. R. A.; Lima, M. C. A.; Araújo, H. D. A.; Marques, D. S. C.; Cruz Filho, I. J. In vitro evaluation of antioxidant, cytotoxic, trypanocidal and antimicrobial activities of lignin obtained from Caesalpinia ferrea leaves and its use as an excipient in the release of oxacillin and fluconazole. International Journal of Biological Macromolecules, v. 250, 126225, 2023. https://doi.org/10.1016/j.ijbiomac.2023.126225

Spiridon, I. Biological and pharmaceutical applications of lignin and its derivatives: A mini-review. Cellulose Chemistry and Technology, v. 52, n. 7/8, p. 543-550, 2018.

Ullah, I.; Chen, Z.; Xie, Y.; Khan, S. S.; Singh, S.; Yu, C.; Cheng, G. Recent advances in biological activities of lignin and emerging biomedical applications: A short review. International Journal of Biological Macromolecules, v. 208, p. 819-832, 2022. https://doi.org/10.1016/j.ijbiomac.2022.03.182

Wang, Y.; Tang, S.; Jiang, L. Yuan, Z.; Zhang, Y. A review of lignin application in hydrogel dressing. International Journal of Biological Macromolecules, v. 281, Part 3, 135786, 2024. https://doi.org/10.1016/j.ijbiomac.2024.135786

Zahirinejad, S.; Ashkan, Z.; Hemmati, R.; Dinari, A.; Jamalidoost, M.; Javanmard, S. H. Efficient biocompatible drug carrier: Lignin-based nanogel amplifies Curcumin's cytotoxic effects and induces apoptosis in brain and lung cancer cell lines. Biocatalysis and Agricultural Biotechnology, v. 60, 103289, 2024. https://doi.org/10.1016/j.bcab.2024.103289

Zhao, J.; Zheng, D.; Tao, Y.; Li, Y.; Wang, L.; Liu, J; He, J.; Lei, J. Self-assembled pH-responsive polymeric nanoparticles based on lignin-histidine conjugate with small particle size for efficient delivery of anti-tumor drugs. Biochemical Engineering Journal, v. 156, 107526, 2020. https://doi.org/10.1016/j.bej.2020.107526

Zhou, J.; Kang, Y.; Chen, L.; Wang, H.; Liu, J.; Zeng, S.; Yu, L. The drug-resistance mechanisms of five platinum-based antitumor agents. Frontiers in Pharmacology, v. 11, 343, 2020. https://doi.org/10.3389/fphar.2020.00343


 

ISSN 2359-1412