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Synthesized‐Chlorotoxin‐Conjugated Cytochrome C as a Potential Drug for Targeting Glioma
Author(s) -
Delinois Louis Jean,
RamirezPaz Josell,
GonzálezFeliciano Jose A.,
MaldonadoHernández Rafael,
BarceloBovea Vanessa,
Joaquin Ovalle Freisa M.,
Fulvio Pasquale F.,
Griebenow Kai
Publication year - 2018
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2018.32.1_supplement.lb99
Subject(s) - cytochrome c , apoptosis , microbiology and biotechnology , biology , chemistry , biochemistry
Amongst primary brain tumors, gliomas are considered the most lethal malignant tumors due to their resistance to radiation and chemotherapy and the difficulty to accurately localize them within the tissue. Chlorotoxin (Ctx), a small neurotoxin of 36 amino acids isolated from the venom of the Israeli scorpion Leiurus quinquestriatus , binds specifically and with high affinity a 72 kDa chloride channel membrane receptor in human gliomas and was proposed to cross the Blood Brain Barrier. These channels are reported to be absent or in low abundance in healthy tissues or in tumors of non‐glial origin. As a component of the scorpion venom, Ctx induces paralysis in small insects or other invertebrates however, no apparent signs of toxicity have been observed when injected in vertebrates. Cytochrome c (CytC), a small membrane impermeable mitochondrial protein (M W = 12 KDa) that facilitates electron transport in cellular respiration, is also known to mediate apoptosis, a normal process of controlled cell death, through the activation of a caspase cascade. In this work, a chemically synthesized‐Ctx is covalently conjugated to CytC through reversible disulfide bridges to accomplish targeted delivery to a glioma cell line 9L/lacZ from Rattus norvegicus and NIH 3T3 from Mus Musculus . Size exclusion chromatography and mass spectrometry characterization of the Ctx‐CytC conjugate show that the Ctx was successfully attached to CytC. Preliminary results from cell viability essay reveal that the Ctx‐Cytc was 40% more toxic than Ctx alone and more toxic to 9L/lacZ than the normal cell line NIH/3T3. These results suggest that the Ctx‐CytC conjugate can be further developed in order to be considered as an alternative potential targeted drug for treatment of gliomas. This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .