Cytotoxic and antitumor properties of methionine γ-lyase conjugate in combination with S-alk(en)yl–L-cysteine sulfoxides

Background. Enzyme prodrug therapy is a promising strategy to treat solid malignancies. The utilization of two-component systems, including an enzyme and non-toxic prodrug, generate cytotoxic compounds directly at the surface tumor cell can be successful in reducing overall toxic load on body. Aim. To determine antitumor activity pharmacological pair C115H methionine γ-lyase (C115H MGL) conjugated with daidzein MGL-Dz) S-alk(en)yl-L-cysteine sulfoxides against various types tumors vitro vivo . Materials. MTT-test was used cytotoxicity MGL-Dz presence Sw620 (colon cancer), Panc1 (pancreatic 22Rv1 (prostate cancer). Apopto- sis induction cycle alteration 22Rv1, Sw620, SKBR3 lines were studied using Muse® Caspase-3/7 Cell Cycle Assay kits. In anticancer Panc1, subcutaneous xenografts Balb/c nude mice. Results. had maximum S-propyl-L-cysteine sulfoxide (propiin) IC 50 values: 3.88 5.4 for respectively. Dipropyl thiosulfinate formed by β-eli-mination propiin catalyzed MGL-Dz, induces apoptosis through both activation caspases alternative pathways, also it inhibits division, contributing decrease concentration cells G 2 /M phase. efficacy C115H-Dz/propiin indicated significant volume (tumor growth inhibition (TGI) 67.5 %, p = 0.004), (TGI 22.07 0.12) 70 0.043). Conclusion. Pharmacological MGL-Dz/propiin capable suppressing development malignant might considered as potential approach cancer therapy.