Cytotoxic and Anticancer Activity of Pharmacological Pairs of C115H Methionine–Gamma-lyase and S-Propyl-L-Cysteine Sulfoxide

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Abstract

BACKGROUND: One of the alternate ways to developing novel medication is to use pharmacological pairs: an enzyme and a non-toxic prodrug that, under certain conditions, releases cytotoxic substances within or on the surface of the cancer cells, allowing the drug to be delivered precisely to the cancer cells.

AIM: To evaluate cytotoxic and anticancer effects of the pharmacological pair of C115H methionine-γ-lyase (C115H MGL), conjugated with daidzein (C115H MGL-Dz), and S-propyl-L-cysteine sulfoxide (propiin) against different kinds of solid tumors in vitro and in vivo.

METHODS: MTT-test was performed to determine the cytotoxicity of C115H MGL-Dz in the presence of 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 PaCa-2) and prostate cancer (DU145, and PC3) cells. The anticancer activity of the pharmacological pair "C115H MGL-Dz + propiin" against SKBR3, MIA PaCa-2, 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 pairs "C115H MGL + propiin", targeted delivery of C115H MGL-Dz as a component of a pharmacological pair "C115H MGL-Dz + propiin" to generate dipropylthiosulfinate directly on the surface of cancer cells enhances cytotoxicity in all cancer cells. 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 PaCa-2 (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 pairs as a novel strategy to cancer treatment.

About the authors

Louay Abo Qoura

Peoples’ Friendship University of Russia; N.N. Blokhin National Medical Research Center of Oncology

Author for correspondence.
Email: louay.ko@gmail.com
ORCID iD: 0000-0001-5391-5077
Russian Federation, 6 Miklukho-Maklaya street, 117198, Moscow; 24 Kashirskoe shosse, Moscow 115478

Saida S. Karshieva

Peoples’ Friendship University of Russia; N.N. Blokhin National Medical Research Center of Oncology

Email: skarshieva@gmail.com
ORCID iD: 0000-0003-2469-2315
SPIN-code: 9154-7071
Russian Federation, 6 Miklukho-Maklaya street, 117198, Moscow; 24 Kashirskoe shosse, Moscow 115478

Julia A. Borisova

Peoples’ Friendship University of Russia; N.N. Blokhin National Medical Research Center of Oncology

Email: ulkabor@yandex.ru
ORCID iD: 0000-0002-0073-7729
SPIN-code: 9757-5847
Russian Federation, 6 Miklukho-Maklaya street, 117198, Moscow; 24 Kashirskoe shosse, Moscow 115478

Vadim S. Pokrovsky

Peoples’ Friendship University of Russia; N.N. Blokhin National Medical Research Center of Oncology

Email: pokrovskiy-vs@rudn.ru
ORCID iD: 0000-0003-4006-9320
SPIN-code: 4552-1226

MD, Dr. Sci. (Med.)

Russian Federation, 6 Miklukho-Maklaya street, 117198, Moscow; 24 Kashirskoe shosse, Moscow 115478

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Supplementary files

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2. Fig. 1. The pharmacological pair «C115H MGL-Dz + propiin» decreases tumor volume in vivo in the nude BALB/c mice with SKBR3 human breast cancer xenografts.

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3. Fig. 2. The pharmacological pair «C115H MGL-Dz + propiin» decreases tumor volume in vivo in the nude BALB/c mice with MIA PaCa-2 pancreatic adenocarcinoma cancer xenografts.

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4. Fig. 3. The pharmacological pair «C115H MGL-Dz + propiin» decreases tumor volume in vivo in the nude BALB/c mice with HT29 colon cancer xenografts.

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