AccScience Publishing / EJMO / Volume 8 / Issue 2 / DOI: 10.14744/ejmo.2024.66593
RESEARCH ARTICLE

Improving the Efficacy of Vincristine for the Treatment of Childhood Acute Lymphoblastic Leukemia in a Murine Model

Gilberto Carlos Franchi Júnior1 Anna Maria Alves de Piloto Fernandes2 Elias Paulo Tessaro3 Phellipe Honório Amaral3 Alexandre Eduardo Nowill1 Valéria Chierice2 Marcos Nogueira Eberlin1 Nasim Bashirichelkasari4 Reza Yadollahvandmiandoab4,5
Show Less
1 Centro Integrado de Pesquisas Oncohematológicas na Infância (CIPOI), UNICAMP, Campinas, São Paulo, Brazil
2 ThoMSon Mass Spectrometry Laboratory, Institute of Chemistry, University of Campinas, UNICAMP, Campinas, São Paulo, Brazil
3 LABMASS – Laboratory, Campinas, São Paulo, Brazil
4 UroScience, School of Medical Sciences, University of Campinas, UNICAMP, Campinas, Sao Paulo, Brazil
5 Department of Biotechnological and Applied Clinical Sciences, University of L’Aquila, L’Aquila, Italy
EJMO 2024, 8(2), 185–193; https://doi.org/10.14744/ejmo.2024.66593
Submitted: 4 December 2023 | Revised: 13 February 2024 | Accepted: 1 May 2024 | Published: 10 July 2024
© 2024 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution -Noncommercial 4.0 International License (CC-by the license) ( https://creativecommons.org/licenses/by-nc/4.0/ )
Abstract

Objectives: Pro-B Acute Lymphoblastic Leukemia (Pro-B ALL) is the most prevalent form of acute leukemia diagnosed in children and represents the most common malignancy of childhood. Despite the advances in the treatment of ALL, many children with ALL suffer from serious side effects of the treatment and even die due to relapse. Therefore, it is necessary to develop more effective but less toxic drugs for the treatment of ALL.

Methods: In the present study we evaluated the antitumor effects of Phosphoethanolamine (Phos), alone and in combination with the chemotherapeutic agent Vincristine (VCR) in an in vivo murine model injected with Pro-B Acute Lymphoblastic Leukemia (Pro-B ALL) and then investigate its effect on the efficacy of chemotherapeutic agent Vincristine (VCR) in combination therapy.

Results: Herein, we showed that although phos is able to increase the percentage of apoptotic leukemic clones sequestered by the spleen, but the ability of phos alone to reduce the percentage of leukemic clones in vivo in peripheral blood of RS4;11 engrafted mice was not observed. Phos showed a synergistic effect on VCR treatment and increased the percentage reduction of leukemic cells compared to treatment with VCR alone. Also, this combined treatment showed VCR 0.1 mg.Kg-1 is able to be as effective as VRC 0.5 mg.Kg-1 treatment in terms of percentage of leukemic cells in peripheral blood.

Conclusion: Phos showed that it can improve the efficiency of VCR and thus reduce the necessary dose for antitumor effect. This suggests its use as an adjuvant agent that may reduce the toxicity associated with cancer treatment.

Keywords
Acute Lymphoblastic Leukemia
Phosphoethanolamine
In Vivo
Murine Model
Vincristine
Conflict of interest
None declared.
References

1. Onciu M. Acute lymphoblastic leukemia. Hematol Oncol Clin North Am 2009;23:655−74.
2. Terwilliger T, Abdul-Hay M. Acute lymphoblastic leukemia: A comprehensive review and 2017 update. Blood Cancer J 2017;7:e577.
3. Pui CH. Acute lymphoblastic leukemia. Pediatr Clin North Am 1997;44:831−46.
4. Harrison CJ, Johansson B. Acute lymphoblastic leukemia. In: Cancer Cytogenetics. Chichester: John Wiley & Sons; 2015. 5. Hunger SP, Mullighan CG. Acute lymphoblastic leukemia in children. New England J Med 2015;373:1541−52.
6. Alvarnas JC, Brown PA, Aoun P, Ballen KK, Barta SK, Borate U, et al. Acute lymphoblastic leukemia. J Natl Compr Canc Netw 2012;10:858−914.
7. Iguchi N, Hecht SL, Gao D, Wilcox DT, Malykhina AP, Cost NG. Sexual dimorphic impacts of systemic vincristine on lower urinary tract function. Sci Rep 2022;12:5113.
8. Dhyani P, Quispe C, Sharma E, Bahukhandi A, Sati P, Attri DC, et al. Anticancer potential of alkaloids: A key emphasis to colchicine, vinblastine, vincristine, vindesine, vinorelbine and vincamine. Cancer Cell Int 2022;22:206.
9. Khodaei M, Mehri S, Pour SR, Mahdavi S, Yarmohammadi F, Hayes AW, et al. The protective effect of chemical and natural compounds against vincristine-induced peripheral neuropathy (VIPN). Naunyn Schmiedebergs Arch Pharmacol 2022;395:907−19.
10. Uittenboogaard A, Neutel CLG, Ket JCF, Njuguna F, Huitema ADR, Kaspers GJL, et al. Pharmacogenomics of vincristineinduced peripheral neuropathy in children with cancer: A systematic review and meta-analysis. Cancers Basel 2022;14:612.
11. Barnett S, Hellmann F, Parke E, Makin G, Tweddle DA, Osborne, et al. Vincristine dosing, drug exposure and therapeutic drug monitoring in neonate and infant cancer patients. Eur J Cancer 2022;164:127−36.
12. Postma TJ, Benard BA, Huijgens PC, Ossenkoppele GJ, Hei mans JJ. Long term effects of vincristine on the peripheral nervous system. J Neurooncol 1993;15:23−7.
13. Duan S, Yu Y, Lai C, Wang D, Wang Y, Xue D, et al. Vincristineloaded and sgc8-modified liposome as a potential targeted drug delivery system for treating acute lymphoblastic leukemia. J Biomed Nanotechnol 2018;14:910−21.
14. Ferreira AK, Santana-Lemos BAA, Rego EM, Filho OMR, Chierice GO, Maria DA. Synthetic phosphoethanolamine has in vitro and in vivo anti-leukemia effects. Br J Cancer 2013;109:2819−28.
15. Mambelli LI, Teixeira SF, Jorge SD, Kawamura B, Meneguelo R, Barbuto JAM, et al. Phosphoethanolamine induces caspaseindependent cell death by reducing the expression of CRAF and inhibits tumor growth in human melanoma model. Biomed Pharmacother 2018;103:18−28.
16. Ferreira AK, Meneguelo R, Claro Neto S, Orivaldo Chierice G, Augusto Maria D. Synthetic phosphoethanolamine induces apoptosis through caspase-3 pathway by decreasing expression of bax/bad protein and changes cell cycle in melanoma. J Cancer Sci Ther 2011;3:3.
17. Ferreira AK, Freitas VM, Levy D, Ruiz JL, Bydlowski SP, Rici RE, et al. Anti-angiogenic and anti-metastatic activity of synthetic phosphoethanolamine. PLoS One 2013;8:e57937.
18. Ferreira AK, Meneguelo R, Marques FL, Radin A, Filho OM, Neto SC, et al. Synthetic phosphoethanolamine a precursor of membrane phospholipids reduce tumor growth in mice bearing melanoma B16-F10 and in vitro induce apoptosis and arrest in G2/M phase. Biomed Pharmacother 2012;66:541−8.
19. Ferreira AK, Meneguelo R, Pereira A, Filho OMR, Chierice GO, Maria DA. Synthetic phosphoethanolamine induces cell cycle arrest and apoptosis in human breast cancer MCF-7 cells through the mitochondrial pathway. Biomed Pharmacother 2013;67:481−7.
20. Luna AC, Saraiva GK, Filho OM, Chierice GO, Neto SC, Cuccovia IM, et al. Potential antitumor activity of novel DODAC/PHO-S liposomes. Int J Nanomed 2016;11:1577−91.
21. Carmo Gallo Netto. Fosfoetanolamina, de ‘pílula do câncer’ a caso de polícia. Available at: https://www.unicamp.br/unicamp/index.php/ju/noticias/2018/04/03/fosfoetanolaminade-pilula-do-cancer-caso-de-policia. Accessed May 3, 2024.
22. Lock RB, Liem N, Farnsworth ML, Milross CG, Xue C, Tajbakhsh M, et al. The nonobese diabetic/severe combined immunodeficient (NOD/SCID) mouse model of childhood acute lymphoblastic leukemia reveals intrinsic differences in biologic characteristics at diagnosis and relapse. Blood 2002;99:4100–8.

Share
Back to top
Eurasian Journal of Medicine and Oncology, Electronic ISSN: 2587-196X Print ISSN: 2587-2400, Published by AccScience Publishing