Antitumor effect of the curaxin CBL0137 on the models of colon cancer

T. I. Fetisov; Фетисов Т. И.; L. R. Tilova; Тилова Л. Р.; E. A. Lesovaya; Лесовая Е. А.; E. E. Antoshina; Антошина Е. Е.; T. G. Gor’kova; Горькова Т. Г.; L. S. Trukhanova; Труханова Л. С.; O. V. Morozova; Морозова О. В.; E. V. Shipaeva; Шипаева Е. В.; R. V. Ivanov; Иванов Р. В.; A. A. Purmal; Пурмаль А. А.; G. A. Belitskiy; Белицкий Г. А.; M. G. Yakubovskaya; Якубовская М. Г.; A. V. Gudkov; Гудков А. В.; K. V. Gurova; Гурова К. В.; K. I. Kirsanov; Кирсанов К. И.

doi:10.17650/2313-805X-2016-3-3-67-72

Antitumor effect of the curaxin CBL0137 on the models of colon cancer

Authors: Fetisov T.I.¹^,2, Tilova L.R.¹^,2, Lesovaya E.A.¹^,3^,4, Antoshina E.E.¹^,2, Gor’kova T.G.¹^,2, Trukhanova L.S.¹^,2, Morozova O.V.¹^,2, Shipaeva E.V.⁵^,6, Ivanov R.V.⁵^,6, Purmal A.A.⁷^,8, Belitskiy G.A.¹^,2, Yakubovskaya M.G.¹^,2, Gudkov A.V.⁷^,8, Gurova K.V.⁷^,8, Kirsanov K.I.¹^,2
Affiliations:
1. N.N. Blokhin Russian Cancer Reseach Center, Ministry of Health of Russia
2. 24 Kashirskoe Shosse, Moscow, 115478, Russia
3. 24 Kashirskoe Shosse, Moscow, 115478, Russia I.P. Pavlov Ryazan’ State Medical University, Ministry of Health of Russia
4. 9 Vasokovol’tnaya St., Ryazan, 390026, Russia
5. LLC Incuron
6. 6 Stolovyy Pereulok, Moscow, 121069, Russia
7. Roswell Park Cancer Institute
8. Buffalo, USA
Issue: Vol 3, No 3 (2016)
Pages: 67-72
Section: RESEARCH ARTICLES
Published: 30.09.2016
URL: https://umo.abvpress.ru/jour/article/view/71
DOI: https://doi.org/10.17650/2313-805X-2016-3-3-67-72
ID: 71

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Abstract

Curaxins represent low molecular weight carbazole derivatives, which simultaneously activate p53-dependent apoptosis and inhibit NF-kBdependent signal transduction pathways. Antitumor activity of curaxin CBL0137 was demonstrated in vivo on the model of solid transplantable mouse colon adenocarcinoma Akatol. Significant tumor growth inhibition caused by CBL0137 treatment was observed. On the 37th day after tumor transplantation for CBL0137 oral doses 5, 10, 15 and 20 mg/kg the tumor growth inhibition indexes were 53, 50, 56 and 74 %, respectively. CBL0137 treatment extended life span of mice in all study groups receiving this test article. Maximum lifespan increase (81,7 %) was observed in the group of mice treated with 20 mg/kg dose of CBL0137. The cytotoxicity of CBL0137 was assessed on human colon cancer cells in vitro. We demonstrated that CBL0137 inhibits the expression COX2, which in its turn is known to exhibit antiapoptotic, pro-angiogenic and pro- metastatic properties. Thus, we demonstrated antitumor effect of CBL0137 against colon cancer in vitro and in vivo.

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colon adenocarcinoma, transplantable tumor, Akatol, curaxin, CBL0137, NF-kB-signal transduction pathway, COX2

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Antitumor effect of the curaxin CBL0137 on the models of colon cancer

Full Text

Abstract

Keywords

About the authors

References

Supplementary files