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

Lyakhova I., Piatkova M., Khotimchenko Y., Zhidkov M., Kantemirov A., Khotimchenko R., Bryukhovetskiy A., Sharma A., Sharma H.S., Bryukhovetskiy I.

В журнале International review of neurobiology

Год: 2020 Номер: 151 Страницы: 325-343

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 15 months. 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 48 Gy 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.

DOI 10.1016/bs.irn.2020.03.011