In vitro modulation of pseudocholinesterase activity by Cu-thiosemicarbazone compounds in rat C6 glioma cells

Abstract

Introduction. Glioma represents one of the most aggressive forms of primary tumors of the central nervous system, characterized by rapid proliferation, high invasiveness, and resistance to conventional therapies. The C6 glioma cell line is a well-established experimental model for investigating molecular mechanisms involved in tumor progression and for testing compounds with potential antineoplastic activity. Pseudocholinesterase (PChE) is a plasma enzyme involved in choline ester metabolism and serves as a biomarker of hepatic function and cellular metabolic status. Cu-thiosemicarbazones are heterocyclic compounds with complex biological activity, including antioxidant and cytotoxic effects. However, their impact on PChE activity in C6 glioma cells has not been fully elucidated. The aim. The study aimed to evaluate the effects of Cu-thiosemicarbazone compounds on PChE activity in C6 glioma cells in vitro and to analyze the concentration-dependent response (10.0 µmol/L and 1.0 µmol/L), using doxorubicin (DOXO) as a reference compound. Materials and Methods. C6 cells were exposed to Cu-thiosemicarbazone compounds (CMA-18, CMD-8, MG-22, CMC-34, CMJ-33, CMT-67, CMG-41, TIA-123, and TIA-160) and to DOXO. PChE activity was measured spectrophotometrically and expressed in µmol/s·L, with statistical descriptors reported as median and interquartile range (IQR). Results were expressed as percentage changes relative to the control group. Results. Data analysis demonstrated a concentration-dependent effect. At 10.0 µmol/L, most compounds produced significant enhancec in PChE activity, the most pronounced being TIA-123 (20%), MG-22, CMT-67, and TIA-160 (17%), followed by CMA-18 and CMJ-33 (12%). At 1.0 µmol/L, the predominant effect was inhibitory, with marked decreases observed for CMT-67 (42%), CMC-34 (35%), and CMJ-33 (31%). DOXO showed a biphasic behavior, with stimulation at the higher concentration and inhibition at the lower concentration. Conclusions. The obtained data indicate significant in vitro modulation of PChE activity by Cuthiosemicarbazone compounds in rat C6 glioma cells in a concentration-dependent manner, with predominant stimulation at 10.0 µmol/L and inhibition at 1.0 µmol/L. These findings suggest potential interactions with plasma esterase metabolism and point toward an anabolic-type effect of the investigated compounds, supporting further studies to elucidate the detailed molecular mechanisms involved.