3-Bromofascaplysin is a prospective chemical compound for developing new chemotherapy agents in glioblastoma treatment

Irina Lyakhova; Mariia Piatkova; Yuri Khotimchenko; Maxim Zhidkov; Alexey Kantemirov; Rodion Khotimchenko; Andrey Bryukhovetskiy; Aruna Sharma; Hari Shanker Sharma; Igor Bryukhovetskiy

doi:10.1016/bs.irn.2020.03.011

3-Bromofascaplysin is a prospective chemical compound for developing new chemotherapy agents in glioblastoma treatment

Int Rev Neurobiol. 2020:151:325-343. doi: 10.1016/bs.irn.2020.03.011. Epub 2020 May 13.

Authors

Affiliations

¹ Department of Fundamental Medicine, School of Biomedicine, Far Eastern Federal University, Vladivostok, Russia; Federal Scientific Center of the East Asia Terrestrial Biodiversity Far Eastern Branch of the Russian Academy of Sciences, Vladivostok, Russia.
² Department of Fundamental Medicine, School of Biomedicine, Far Eastern Federal University, Vladivostok, Russia.
³ Department of Fundamental Medicine, School of Biomedicine, Far Eastern Federal University, Vladivostok, Russia; Laboratory of Pharmacology, National Scientific Center of Marine Biology, Far East Branch of the Russian Academy of Sciences, Vladivostok, Russia.
⁴ Department of Organic Chemistry, School of Natural Sciences, Far Eastern Federal University, Vladivostok, Russia.
⁵ Laboratory of Pharmacology, National Scientific Center of Marine Biology, Far East Branch of the Russian Academy of Sciences, Vladivostok, Russia.
⁶ NeuroVita Clinic of Interventional and Restorative Neurology and Therapy, Moscow, Russia.
⁷ International Experimental Central Nervous System Injury & Repair (IECNSIR), Department of Surgical Sciences, Anesthesiology & Intensive Care Medicine, University Hospital, Uppsala University, S-75185 Uppsala, Sweden.
⁸ Department of Fundamental Medicine, School of Biomedicine, Far Eastern Federal University, Vladivostok, Russia; Laboratory of Pharmacology, National Scientific Center of Marine Biology, Far East Branch of the Russian Academy of Sciences, Vladivostok, Russia. Electronic address: igbryukhovetskiy@gmail.com.

PMID: 32448614
DOI: 10.1016/bs.irn.2020.03.011

Abstract

Glioblastoma (GB) is one of the most aggressive human brain tumors. The prognosis is unfavorable, its treatment is relatively ineffective, and the median survival is about 15months. Medication development with new chemical compounds is one of the ways to solve the problem of current treatment inefficiency. This study is focused on the group of chemical substances, based on pentacyclic system of 12H-pyrido[1,2-a:3,4-b]diindole, and the most well-known part of this group is fascaplysin, first extracted from the sponge Fascaplysinopsis spp. We have synthesized a series of the following fascaplysin derivatives: 7-phenylfascaplysin, 3-chlorofascaplysin, 3-bromofascaplysin, 9-bromofascaplysin. The paper is aimed at analyzing the cytotoxic effect of these compounds on GB cells.

Materials and methods: The study used rat glioma C6 cell line (ATCC®; cat no CCL-107), U-87MG cell line (ATCC; cat no. HTB-14™) and human glioblastoma T98-G cells (ATCC® CRL-1690™). Cell culture method, experimental pharmacological trials and γ-radiation in vitro, as well as flow cytofluorometry were used in the study.

Results: Cytotoxic effect of the tested compounds is stronger than the effect of unsubstituted fascaplysin, and appears to be dose-dependent and time-dependent. 3-bromofascaplysin is more efficient for cancer cells elimination, and by the end of the experiment the amount of living cancer cells in G₀ phase remained at its lowest. Cytotoxic effect of 3-bromofascaplysin on glioblastoma T98-G cells is inferior to that of TMZ, and in case of preliminary radiation treatment of cancer cells with 48Gy the effect of the compound matches the TMZ treatment results.

Conclusion: 3-Bromofascaplysin is a prospective chemical compound for development of new anti-cancer chemotherapeutic agents.

Keywords: 3-Bromofascaplysin; Chemotherapy; Fascaplysin; Glioblastoma; Radiation treatment.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Antineoplastic Agents / pharmacology*
Brain Neoplasms / drug therapy*
Brain Neoplasms / radiotherapy*
Cell Line, Tumor
Glioblastoma / drug therapy*
Glioblastoma / radiotherapy*
Humans
Indoles / pharmacology*
Rats

Substances

Antineoplastic Agents
Indoles
fascaplysine