A new indolocarbazole derivative in melanoma and carcinoma lung in vivo treatment
Tóm tắt
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. 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. 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. 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.
Tài liệu tham khảo
Denny WA. Emerging DNA topoisomerase inhibitors as anticancer drugs. Expert Opin Emerg Drugs. 2004;9(1):105–33. https://doi.org/10.1517/eoed.9.1.105.32948.
Xu Y, Her C. Inhibition of topoisomerase (DNA) I (TOP1): DNA damage repair and anticancer therapy. Biomolecules. 2015;5(3):1652–70. https://doi.org/10.3390/biom5031652.
Borisova LM, Golubeva IS, Gorjunova OV, Eremina VA, Zhukova OS et al. N-Glycosides of indolo [2,3-a]pyrrolo [3,4-c] carbazoles having antitumor activity. Patent RF, no 2548045, 2014. Available from: https://www1.fips.ru/registers-doc-view/fips_servlet?DB=RUPAT&DocNumber=2548045&TypeFile=html.
Vartanjan AA, Baryshnikova MA, Eremina VA, Miniker TD, Tikhonova NI, Kuz'mina NE, Ehktova LV. Indolocarbazole derivative blocking tumors vasculogenic mimicry. Patent RF. no 2557554, 2014. Available from: https://www1.fips.ru/registers-doc-view/fips_servlet?DB=RUPAT&DocNumber=2557554&TypeFile=html.
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, Stepanova E, Grigorieva I, Solomka E, Baryshnikov A, Lichinitser M. VEGFR1 and PKCα signaling control melanoma vasculogenic mimicry in a VEGFR2 kinase-independent manner. Melanoma Res. 2011;21(2):91–8. https://doi.org/10.1097/CMR.0b013e328343a237.
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.
Hendrix MJ, Sefror EL, Hess AR, Seftor REB. Molecular plasticity of human melanoma cells. Oncogene. 2003;22(20):3070–5. https://doi.org/10.1038/sj.onc.1206447.
Azam F, Shavets M, Harris AD. Mechanisms of resistance to Antiangiogenesis therapy. Eur J Cancer. 2010;46(8):1323–32. https://doi.org/10.1016/j.ejca.2010.02.020.
Plas DR, Thompson CB. Akt-dependent transformation: there is more to growth than just surviving. Oncogene. 2005;24(50):7435–42. https://doi.org/10.1038/sj.onc.1209097.
Vartanian A, Gatsina G, Grigorieva I, Solomko E, Dombrovsky V, Baryshnikov A, et al. The involvement of notch signaling in melanoma vasculogenic mimicry. Clin Exp Med. 2013;13(3):201–9. https://doi.org/10.1007/s10238-012-0190-9.
Senderowicz AM. Inhibitors of cyclin-dependent kinase modulators for cancer therapy. Prog Drug Res. 2005;63:183–206. https://doi.org/10.1007/3-7643-7414-4_8.
Vartanian AA, Burova OS, Stepanova EV, Baryshnikov AY, Lichinitser MR. Melanoma vasculogenic mimicry is strongly related to reactive pxygen species level. Melanoma Res. 2007;17(6):370–9. https://doi.org/10.1097/cmr.0b013e3282f1d2ec.
Nock CJ, Brell JM, Bokar JA, Cooney MM, Cooper B, Gibbons J, et al. A phase I study of rebeccamycinanalog in combination with oxaliplatin in patients with refractory solid tumors. Investig New Drugs. 2011;29(1):126–30. https://doi.org/10.1007/s10637-009-9322-9.
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.
Oh Y, Herbst RS, Burris H, Cleverly A, Musib L, Lahn M, et al. Еnzastaurin, an oral, serine/threonine kinase inhibitor, as second- or third-line therapy of non-small cell lung cancer. J Clin Oncol. 2008;26(7):1135–41. https://doi.org/10.1200/JCO.2007.14.3685.
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.
Mirzaei H, Sahebkar A, Avan A, Jaafari MR, Salehi R, et al. Application of mesenchymal stem cells in melanoma: a potential therapeutic strategy for delivery of targeted agents. Curr Med Chem. 2016;23(5):455–63. https://doi.org/10.2174/0929867323666151217122033.
Pourhanifeh MH, Abbaszadeh-Goudarzi K, Goodarzi M, Piccirillo SGM, Shafiee A, Hajighadimi S, et al. Resveratrol: a new potential therapeutic agent for melanoma? Curr Med Chem. 2021;28(4):687–711. https://doi.org/10.2174/0929867326666191212101225.
Mirzaei H, Salehi H, Oskuee RK, Mohammadpour A, Mirzaei HR, Sharifi MR, et al. The therapeutic potential of human adipose-derived mesenchymal stem cells producing CXCL10 in a mouse melanoma lung metastasis model. Cancer Lett. 2018;10(419):30–9. https://doi.org/10.1016/j.canlet.2018.01.029.
Mardani R, Hamblin MR, Taghizadeh M, Banafshe HR, Nejati M, Mokhtari M, et al. Nanomicellar-curcumin exerts its therapeutic effects via affecting angiogenesis, apoptosis, and T cells in a mouse model of melanoma lung metastasis. Pathol Res Pract. 2020;216(9):153082. https://doi.org/10.1016/j.prp.2020.153082.
Davoodvandi A, Darvish M, Borran S, Nejati M, Mazaheri S, Reza Tamtaji O, et al. The therapeutic potential of resveratrol in a mouse model of melanoma lung metastasis. Int Immunopharmacol. 2020;88:106905. https://doi.org/10.1016/j.intimp.2020.106905.
Amiri A, Pourhanifeh MH, Mirzaei HR, Nahand JS, Moghoofei M, Sahebnasagh R, et al. Exosomes and lung Cancer: roles in pathophysiology, diagnosis and therapeutic applications. Curr Med Chem. 2021;28(2):308–28. https://doi.org/10.2174/0929867327666200204141952.
Bol'shakov OP, Neznanov NG, Babakhanyan RV. Didactic and ethical aspects of research on biomodels and laboratory animals. Kachestvennaya Klinicheskaya Praktika. 2002;1:58–61 https://www.clinvest.ru/jour/article/view/249#tab1.
Софьина З.П., Сыркин АБ. Экспериментальная оценка противоопухолевых веществ в СССР и США. Москва: Медицина; 1980 г.
Миронов А.Н., редактор. Руководство по доклиническим исследованиям лекарственных средств, часть 1. М .: Гриф и К; 2012. с. 642–57.
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 .