Combination of lithium chloride and pEGFP-N1-BmK CT effectively decreases proliferation and migration of C6 glioma cells

Abstract

Deleterious invasiveness of glioma cells into the normal brain tissue is endorsed by its inherent ability to regulate the receptor-mediated adhesive properties, extracellular matrix degradation and remodeling and elevated secretory ability of metalloproteinase (MMPs) such as MMP-2. By doing so, it will create an intercellular space for the invasion of glioma cells. Here, we reported that combination of gene therapy Buthus martensii Karsch (BmK) CT, a type of scorpion toxin peptide, with lithium chloride (LiCl), clinically used as mood stabilizer, could inhibit the migration and invasion of C6 glioma cells. The results showed that concomitant administration of LiCl and pEGFP-N1-BmK CT on glioma cells would hamper pro-MMP2 secretion and in the meantime, inhibited its proliferation in a synergistic manner. These results try to extrapolate the potential interplay between the combined treatment of LiCl and BmK CT with signaling pathways β-catenin, MMP, GSK-3 in C6 glioma cells. This strategy can stand for a novel approach designated for the development of a new method for glioma therapy.

Ultrastructural and Immunofluorescent Analysis of Lithium Effects on Autophagy in Hepatocellular Carcinoma Cells

“…It has been shown that lithium is effective in inhibiting glioma [31], esophageal cancer [32], pancreatic cancer [33], colorectal cancer [34], leukemia and other cancer cells; and several studies suggested the beneficial effects of lithium on cancer cell death and autophagy. O'Donovan et al [36] have demonstrated that lithium-treated colorectal cells showed autophagosomes formation and vesicle accumulation.…”

Scorpion venoms and associated toxins as anticancer agents: update on their application and mechanism of action

“…Gu, Liu, Ju, Li, and Cao (2012) reported the anticancer trait of recombinant analgesic‐antitumor peptide (rAGAP) toxin (isolated from the B. martensii Karsch venom) against the SW‐480 cell line (colorectal adenocarcinoma) and reported a mortality rate of 78.8% with an IC 50 value of 8.4 μM. Fu, Jiao, Zheng, Liang, and Hu (2014) transfected the plasmid pEGFP‐N1‐BmK (4.0 μg of DNA), containing the BmK CT gene (isolated from B. martensii Karsch) into rat glioma C6 cells. Subsequently, the therapeutic agent LiCl (50 mM), which inhibits migration and invasion in glioma cells, was added as a co‐treatment, obtaining 75% cytotoxicity within 24 h. Song et al (2012) purified SVIII toxin from B. martensii Karsch venom and investigated its anticancer potential against the THP‐1 (acute monocytic leukemia) and Jurkat cell lines (acute T cell leukemia), obtaining 66.6% (IC 50 value: 50 μg/mL) and 58.7% (IC 50 value: 50 μg/mL) of cytotoxicity, respectively.…”

Review on Bioactive Peptides and Pharmacological Activities of Buthus martensii Karsch

“…Zeng et al [7] Cao et al [8] Gao et al [9] Inhibiting the glioma cell migration in vitro BmK CT Fu et al [13][14][15][16] Antitumor against Ehrlich ascites and S-180 fibrosarcoma in vitro BmK AGAP-SYPU2 Shao et al [17] Antinociceptive activity in vivo…”

“…Subsequently, Yuejun Fu et al [15] found pEGFP-N1 mediated BmK CT expression displayed a significant suppression in migration of rat glioma C6 cells by in vitro studies. Moreover, Yuejun Fu et al [16] also performed a study to observe the combination of gene therapy pEGFP-N1-BmK CT with lithium chloride (LiCl) on C6 glioma cells. They reported that the combination therapy could inhibit the secretion and proliferation of pro-MMP2 in a synergistic manner, which might provide a new therapeutic strategy for glioma cancer.…”