Methionine γ-Lyase-Daidzein in Combination with S-Propyl-L-cysteine Sulfoxide as a Targeted Prodrug Enzyme System for Malignant Solid Tumor Xenografts
Louay Abo Qoura; Elena Morozova; Vitalia Kulikova; Saida Karshieva; Darina Sokolova; Vasiliy Koval; Svetlana Revtovich; Tatyana Demidkina; Vadim S. Pokrovsky
The purpose of this study was to determine the anticancer effect of dipropyl thiosulfinate produced in situ by the pharmacological pair: (1) conjugated with daidzein C115H methionine &gamma:-lyase (EC 4.4.1.11, C115H MGL-Dz) and (2) the substrate, S-propyl-L-cysteine sulfoxide (propiin) against various solid tumor types in vitro and in vivo. The MTT test was used to calculate IC50 values for HT29, COLO205 and HCT116 (colon cancer): Panc1 and MIA-PaCa2 (pancreatic cancer): and 22Rv1, DU-145 and PC3 (prostate cancer). The most promising effect for colon cancer cells in vitro was observed in HT29 (IC50 = 6.9 µ:M). The IC50 values for MIA-PaCa2 and Panc1 were 3.4 and 3.8 µ:M, respectively. Among prostate cancer cells, 22Rv1 was the most sensitive (IC50 = 5.4 µ:M). In vivo antitumor activity of the pharmacological pair was studied in HT29, SW620, Panc1, MIA-PaCa2 and 22Rv1 subcutaneous xenografts in BALB/c nude mice. The application of C115H MGL-Dz /propiin demonstrated a significant reduction in the tumor volume of Panc1 (TGI 67%: p = 0.004), MIA-PaCa2 (TGI 50%: p = 0.011), HT29 (TGI 51%: p = 0.04) and 22Rv1 (TGI 70%: p = 0.043) xenografts. The results suggest that the combination of C115H MGL-Dz/propiin is able to suppress tumor growth in vitro and in vivo and the use of this pharmacological pair can be considered as a new strategy for the treatment of solid tumors.
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