α-Conotoxins and α-Cobratoxin Promote, while Lipoxygenase and Cyclooxygenase Inhibitors Suppress the Proliferation of Glioma C6 Cells

Abstract

Among the brain tumors, glioma is the most common. In general, different biochemical mechanisms, involving nicotinic acetylcholine receptors (nAChRs) and the arachidonic acid cascade are involved in oncogenesis. Although the engagement of the latter in survival and proliferation of rat C6 glioma has been shown, there are practically no data about the presence and the role of nAChRs in C6 cells. In this work we studied the effects of nAChR antagonists, marine snail α-conotoxins and snake α-cobratoxin, on the survival and proliferation of C6 glioma cells. The effects of the lipoxygenase and cyclooxygenase inhibitors either alone or together with α-conotoxins and α-cobratoxin were studied in parallel. It was found that α-conotoxins and α-cobratoxin promoted the proliferation of C6 glioma cells, while nicotine had practically no effect at concentrations below 1 µL/mL. Nordihydroguaiaretic acid, a nonspecific lipoxygenase inhibitor, and baicalein, a 12-lipoxygenase inhibitor, exerted antiproliferative and cytotoxic effects on C6 cells. nAChR inhibitors weaken this effect after 24 h cultivation but produced no effects at longer times. Quantitative real-time polymerase chain reaction showed that mRNA for α4, α7, β2 and β4 subunits of nAChR were expressed in C6 glioma cells. This is the first indication for involvement of nAChRs in mechanisms of glioma cell proliferation.

Multi-omics profiling reveals Chitinase-3-like protein 1 as a key mediator in the crosstalk between sarcopenia and liver cancer

“…we also performed targeted oxylipin profiling, and identified activated AA metabolism by CHI3L1. The compounds of the cascade, such as prostaglandin E2 and leukotrienes, is known for their capability supporting cancer cell survival and proliferation [ 46 ]. Here we concluded that CHI3L1 promotes ROS synthesis and disturbs lipid homeostasis, thus accelerating HCC progression.…”

Interaction of α9α10 Nicotinic Receptors With Peptides and Proteins From Animal Venoms

“…The application of α-conotoxins PnIA, RgIA, ArIB[V11L,V16D], or MII together with either baicalein or indomethacin to Ehrlich carcinoma enhanced the antitumor activity several-fold ( Osipov et al, 2020 ). However, while baicalein exerted antiproliferative and cytotoxic effects also on C6 glioma cells, α-Ctx and α-conotoxin RgIA on the contrary promoted proliferation of these cells ( Terpinskaya et al, 2021 ). Thus, further research is required to elucidate the role of nAChRs in different tumor cell lines and environments.…”

Marine natural products

“…655 α-Conotoxins promote the proliferation of C6 glioma cells in vitro . 656 Synthesised 3/4- and 3/6-, but not 3/7-, loop-size variants of α-conotoxins GI and MI are potent inhibitors of muscular nAChR's. 657 Both the α4/7-conotoxin CIC (venom of C. catus ) and an N -terminus truncated mutant selectively inhibit α3β2 and α6/α3β2β3 nAChR, suggesting the N -terminal tail can accommodate structural changes without any effect on observed receptor activity.…”