Recombinant SLURP-1 Inhibits Growth and Migration of U251 MG Glioma by Cell Cycle Arrest and Modulation of MAPK and AKT Signaling Pathways

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Abstract

A recombinant analog of the human SLURP-1 protein (rSLURP-1) effectively inhibits the growth of carcinomas by interaction with the α7-type nicotinic acetylcholine receptor. Recently, rSLURP-1 inhibition of gliomas growth in vitro was shown by the authors, although, the mechanism of rSLURP-1 action was not studied. Here, we showed that rSLURP-1 selectively inhibits the growth of U251 MG glioma cells but not of normal astrocytes, and controls glioma cell migration. In addition, rSLURP-1 induces cell cycle arrest in the G2/M phase in U251 MG glioma cells, but does not result in apoptosis. Incubation of U251 MG cells with rSLURP-1 causes inhibition of phosphorylation of ERK, p38 MAPK, and AKT kinases, the activation of which contributes to the progression of gliomas. At the same time, rSLURP-1 does not affect the activity of JNK kinase. Thus, rSLURP-1 is an endogenous protein promising for the development of drugs based on it for the treatment of not only carcinomas, but also gliomas.

About the authors

M. A. Shulepko

Shenzhen MSU-BIT University, International University Park Road 1; Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences

Email: ekaterina-lyukmanova@yandex.ru
PRC, 518172, Guangdong Province, Shenzhen, Dayun New Town, Longgang District; Russia, 117997, Moscow, ul. Miklukho-Maklaya 16/10

M. L. Bychkov

Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences

Email: ekaterina-lyukmanova@yandex.ru
Russia, 117997, Moscow, ul. Miklukho-Maklaya 16/10

M. P. Kirpichnikov

Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences; Interdisciplinary Scientific and Educational School of Moscow University “Molecular Technologies of the Living Systems and Synthetic Biology”, Faculty of Biology, Lomonosov Moscow State University

Email: ekaterina-lyukmanova@yandex.ru
Russia, 117997, Moscow, ul. Miklukho-Maklaya 16/10; Russia, 119234, Moscow, Leninskiye Gory 1/12

E. N. Lyukmanova

Shenzhen MSU-BIT University, International University Park Road 1; Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences; Interdisciplinary Scientific and Educational School of Moscow University “Molecular Technologies of the Living Systems and Synthetic Biology”, Faculty of Biology, Lomonosov Moscow State University

Author for correspondence.
Email: ekaterina-lyukmanova@yandex.ru
PRC, 518172, Guangdong Province, Shenzhen, Dayun New Town, Longgang District; Russia, 117997, Moscow, ul. Miklukho-Maklaya 16/10; Russia, 119234, Moscow, Leninskiye Gory 1/12

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