Toxin from black mamba venom inhibits growth of glioma cells selectively expressing ASIC1a channels

The researchers from the IBCh RAS together with the collaborators from the Institute of Cytology RAS demonstrated for the first time the expression of functionally active ASIC1a channels in U251 MG and A172 gliomas cells, but not in normal astrocytes. A recombinant analogue of mambalgin-2 from black mamba venom was used to suppress the cation influx through ASIC1a channels in glioma cells. As it turned out, mambalgin-2 inhibits the growth of gliomas with EC 50 in the nanomolar range, while not affecting the proliferation of normal astrocytes. Mutant variants of mambalgin-2 with impaired affinity for ASIC1a did not affect the proliferation of glioma cells. It was shown that the decrease in the growth of gliomas cells using mambalgin-2 is associated with the cell cycle arrest, inhibition of phosphorylation of cyclin D1 and cyclin-dependent kinases, and apoptosis induction. The study was published in the Cancers journal under support of the Russian Foundation for Basic Research. Learn more

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  • Toxin from black mamba venom inhibits growth of glioma cells selectively expressing ASIC1a channels science news VII.20

    Gliomas are fast growing and highly invasive brain tumors, characterized by tumor microenvironment acidification that drives glioma cell growth and migration. Channels containing Acid-sensing Ion Channel 1a subunit (ASIC1a) mediate amiloride-sensitive cation influx in late stage glioma cells, but not in normal astrocytes. Thus, selective targeting of ASIC1a can be a perspective strategy for glioma treatment.

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    Researchers from IBCh RAS together with their international collаborators discovered an evolutionary link between efficiency of start codons and the probability of AUG codon occurrence in the 5'-end parts of protein-coding sequences. When start codons are inefficient the next AUG codon is more likely to be found in the same reading frame. At the same time in case of highly efficient start codons, the next AUG codon is more likely to be found in alternative frames. They also have shown that weak initiation at the first starts is associated with the synthesis of shortened proteoforms as a result of initiation at the second starts.

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    A collaboration of scientists from the Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, the Moscow Institute of Physics and Technology and Prokhorov General Physics Institute of the Russian Academy of Sciences have developed a breakthrough technology to resolve a key problem that has prevented the introduction of novel drugs into clinical practice for decades. The study was published in Nature Biomedical Engineering and featured in the journal’s News & Views section.

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