CYTOTOXIC AND ANTICANCER ACTIVITIES OF PHARMACOLOGICAL PAIRS C115H METHIONINE GAMMA-LYASE AND S-PROPYL-L-CYSTEINE SULFOXIDE

Abstract

BACKGROUND: One of the alternate ways to developing novel medication is pharmacological pairs: an enzyme and a non-toxic prodrug that, under certain conditions, release cytotoxic substances within or on the surface of the cancer cells, allowing the drug to be delivered precisely to the cancer cells. AIMS: To evaluate cytotoxic and anticancer effects of the pharmacological pair C115H methionine -lyase (C115H MGL), conjugated with daidzein (C115H MGL-Dz), and S-propyl-L-cysteine sulfoxide against different kinds of solid tumors in vitro and in vivo. MATERIALS AND METHODS: MTT-test was performed to determine the cytotoxicity of C115H MGL-Dz in the presence of S-propyl-L-cysteine sulfoxide (propiin) in vitro against human embryonic kidney (HEK-293), human placenta, breast cancer (MCF7, SKBR3, and T47D), colon cancer (HT29 and COLO205), pancreatic cancer (MIA PaCa2) and prostate cancer (DU145, and PC3) cells. The anticancer activity of the pharmacological pair C115H MGL-Dz + propiin against SKBR3, MIA PaCa2, and HT29 in vivo was investigated using subcutaneous xenografts in Balb/c nude mice. RESULTS: In comparison to dipropylthiosulfinate generated in vitro using the pharmacological pairsC115H MGL + propiin, targeted delivery of C115H MGL-Dzas a component of a pharmacological pair C115H MGL-Dz + propiin to generatedipropylthiosulfinate directly on the surface of cancercells enhances cytotoxicity in all cancercells. The study of the antitumor activity of the pharmacological pair C115H MGL-Dz + propiin in vivo revealed a suppression of tumor volume growth in xenografts SKBR3 (tumor growth inhibition (TGI) 89%, p = 0.004), MIA PaCa2 (TGI 50%, p = 0.011), and HT29 (TGI 52%, p = 0.04) vs control. CONCLUSIONS: On several cancer cells, the cytotoxicity and anticancer activity of dipropylthiosulfinate produced by the pharmacological pair C115H MGL-Dz + propiin was observed. Our findings may stimulate more study into the role of pharmacological pairsas a novel strategy to cancer treatment.