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Published in: BMC Complementary Medicine and Therapies 1/2021

Open Access 01-12-2021 | Melanoma | Research article

A new indolocarbazole derivative in melanoma and carcinoma lung in vivo treatment

Authors: Anna Lantsova, Irina Golubeva, Larisa Borisova, Lyudmila Nikolaeva, Lydia Ektova, Maria Dmitrieva, Olga Orlova

Published in: BMC Complementary Medicine and Therapies | Issue 1/2021

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Abstract

Objective

The current scientific research direction is development of drugs with a targeted effect on malignant tumors. One of the promising groups is indolocarbazoles and their derivatives, which can initiate various tumor cell death pathways. Russian scientists from N. N. Blokhin National Medical Research Center of Oncology of the Ministry of Health of Russian Federation has developed a new experimental drug form of the original compound LCS 1269 with cytotoxic and antiangiogenic properties, blocking vasculogenic mimicry in tumor. The study aim is the experimental drug form LCS 1269 antitumor activity on models of transplantable mouse tumors B-16 melanoma and Lewis epidermoid lung carcinoma (LLC) with different routes and modes of administration.

Material and methods

Female F1 hybrid mice (C57Bl/6 x DBA/2) and male and female linear mice C57BL/6 were used for management of tumor strains. Mice were obtained from N. N. Blokhin National Medical Research Center of Oncology of the Ministry of Health of Russian Federation vivarium. The antitumor effect was assessed by tumor growth inhibition (TGI) and increase of treated animal’s life span (ILS) compared to the control.

Results

The experimental drug form showed high antitumor activity when administered intravenously once at doses of 100 and 120 mg/kg (TGI = 98–82% and TGI = 95–77%, respectively, ILS = 24%, p < 0.05) on melanoma B-16 mice. On LLC mice, the experimental drug form showed that the intravenous administration route was effective in the range of doses from 60 to 80 mg/kg with a 5 day administration regimen with an interval of 24 h. A dose of 70 mg/kg had maximum effect at the level of TGI = 96–77% (p < 0.05) with its retention for 20 days after the end of treatment.

Conclusion

The studies have shown that the new compound LCS 1269 in the original drug form, has a pronounced antitumor activity and significantly reduces the volume of tumor mass both on melanoma B-16 and on LLC. It allows us to recommend continue the search for sensitivity of animal transplantable tumors to LCS 1269.
Literature
5.
go back to reference Vartanian A, Golubeva I, Shprakh Z. Is Vasculogenic mimicry a Hallmark of an aggressive tumors? In “horizons in Cancer research”. NY Nova Sci Publishers. 2017;65:13–34. Vartanian A, Golubeva I, Shprakh Z. Is Vasculogenic mimicry a Hallmark of an aggressive tumors? In “horizons in Cancer research”. NY Nova Sci Publishers. 2017;65:13–34.
7.
go back to reference Vartanian A, Baryshnikov A. Molecular determinants of tumorvasculogenic mimicry. In: Melanoma: molecular biology, risk factors and treatment options. USA: Nova Science Publishers; 2013. p. 67–92. Vartanian A, Baryshnikov A. Molecular determinants of tumorvasculogenic mimicry. In: Melanoma: molecular biology, risk factors and treatment options. USA: Nova Science Publishers; 2013. p. 67–92.
15.
go back to reference Saulnierv MG, Balasubramanian BN, Long BH, Frennesson DB, Ruediger E, Zimmermann K, et al. Discovery of a fluoroindolo [2,3-a] carbazole clinical candidate with broad spectrum antitumor activity in preclinical tumor models superior to the marketed oncology drug, CPT-11. J Med Chem. 2005;48(7):2258–61. https://doi.org/10.1021/jm049090z.CrossRef Saulnierv MG, Balasubramanian BN, Long BH, Frennesson DB, Ruediger E, Zimmermann K, et al. Discovery of a fluoroindolo [2,3-a] carbazole clinical candidate with broad spectrum antitumor activity in preclinical tumor models superior to the marketed oncology drug, CPT-11. J Med Chem. 2005;48(7):2258–61. https://​doi.​org/​10.​1021/​jm049090z.CrossRef
17.
go back to reference Pereira ER, Belin L, Sancelme M, Prudhomme M, Ollier M, Rapp M, et al. Structure – activity relationships in a series of substituted indolocarbazoles: topoisomerase I and protein kinase C ingibition and antitumoral and antimicrobial properties. J Med Chem. 1996;39(22):4471–7. https://doi.org/10.1021/jm9603779.CrossRefPubMed Pereira ER, Belin L, Sancelme M, Prudhomme M, Ollier M, Rapp M, et al. Structure – activity relationships in a series of substituted indolocarbazoles: topoisomerase I and protein kinase C ingibition and antitumoral and antimicrobial properties. J Med Chem. 1996;39(22):4471–7. https://​doi.​org/​10.​1021/​jm9603779.CrossRefPubMed
25.
go back to reference Софьина З.П., Сыркин АБ. Экспериментальная оценка противоопухолевых веществ в СССР и США. Москва: Медицина; 1980 г. Софьина З.П., Сыркин АБ. Экспериментальная оценка противоопухолевых веществ в СССР и США. Москва: Медицина; 1980 г.
26.
go back to reference Миронов А.Н., редактор. Руководство по доклиническим исследованиям лекарственных средств, часть 1. М .: Гриф и К; 2012. с. 642–57. Миронов А.Н., редактор. Руководство по доклиническим исследованиям лекарственных средств, часть 1. М .: Гриф и К; 2012. с. 642–57.
27.
go back to reference Киселева М.П., Шпрах З.С., Борисова Л.М., Кубасова И.Ю., Ланцова А.В., Санарова Е.В. и др. Доклиническое исследование противоопухолевой активности производного N-гликозидов индолокарбазолов LCS-1208. Отчет I. Russ J Biother. 2015; 14 (2): 71–7. https://doi.org/10.17650/1726-9784-2015-14-2-71-77 . Киселева М.П., ​​Шпрах З.С., Борисова Л.М., Кубасова И.Ю., Ланцова А.В., Санарова Е.В. и др. Доклиническое исследование противоопухолевой активности производного N-гликозидов индолокарбазолов LCS-1208. Отчет I. Russ J Biother. 2015; 14 (2): 71–7. https://​doi.​org/​10.​17650/​1726-9784-2015-14-2-71-77 .
Metadata
Title
A new indolocarbazole derivative in melanoma and carcinoma lung in vivo treatment
Authors
Anna Lantsova
Irina Golubeva
Larisa Borisova
Lyudmila Nikolaeva
Lydia Ektova
Maria Dmitrieva
Olga Orlova
Publication date
01-12-2021
Publisher
BioMed Central
Keywords
Melanoma
Melanoma
Published in
BMC Complementary Medicine and Therapies / Issue 1/2021
Electronic ISSN: 2662-7671
DOI
https://doi.org/10.1186/s12906-021-03294-2

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