Fascaplysinis a promising agent for the creation of new treatments' methods of glial brain tumors



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Abstract

The effectiveness of glial brain tumors treatment remains low. Standard treatments do not provide a radical removal of tumor cells infiltrating the brain substance. One solution to this problem is to find new compounds with high anti-tumor activity and the methods' development of targeted delivery. Our attention was drawn to a group of compounds, which are based on pentacyclic system of pyrido[1,2-a: 3,4-b'] diindols. The most famous representative is fascaplysin. It is the first substance isolated from a marine sponge Fascaplysynopsis sp. The objective was to explore the characteristics and mechanisms of the cytotoxic and cytostatic effect of fascaplysin on C6 glioma cells in vitro, and to compare the effectiveness fascaplysin and temozolomide in vitro and in a targeted delivery to the tumor in vivo. We used techniques: mammalian cell cultures, high-performance robotic quantitative microscopy, confocal laser fluorescence microscopy, flow cytometry, modeling of glioblastoma in vivo, pharmacological testing, magnetic resonance imaging. It is shown that fascaplysin induces apoptosis in C6 glioma cells. At a concentration of 2 uMfascaplysin was more effective than the temozolomide. Decrease of concentration below 0.5 uM resulted to reduction of cytotoxic effects. The severity of cytostatic effect increased with increasing exposure time. Targeted delivery the fascaplysin to the tumor using transport capacity of stem cells increased the lifespan of rats and decrease in tumor size.

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About the authors

I. S Bryukhovetskiy

School of Biomedicine, Far Eastern Federal University;A.V. Zhirmunsky Institute of Marine Biology, Far Eastern Branch of the RAS.

Vladivostok, Russia

M. E Zhidkov

School of Biomedicine, Far Eastern Federal University.

Vladivostok, Russia.

I. V Kudryavtsev

School of Biomedicine, Far Eastern Federal University.

Vladivostok, Russia.

A. V Polevshikov

School of Biomedicine, Far Eastern Federal University.

Vladivostok, Russia.

P. V Mishchenko

A.V. Zhirmunsky Institute of Marine Biology, Far Eastern Branch of the RAS;School of Biomedicine, Far Eastern Federal University

Vladivostok, Russia

E. V Milkina

A.V. Zhirmunsky Institute of Marine Biology, Far Eastern Branch of the RAS;School of Biomedicine, Far Eastern Federal University

Vladivostok, Russia

A. S Bryukhovetskiy

School of Biomedicine, Far Eastern Federal University

Vladivostok, Russia

S. V Zaitsev

School of Biomedicine, Far Eastern Federal University

Vladivostok, Russia

IA. A Lyahova

School of Biomedicine, Far Eastern Federal University

Vladivostok, Russia

V. V Vikhareva

School of Biomedicine, Far Eastern Federal University

Vladivostok, Russia

Yu. S Khotimchenko

A.V. Zhirmunsky Institute of Marine Biology, Far Eastern Branch of the RAS; School of Biomedicine, Far Eastern Federal University

Vladivostok, Russia

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