Benzyl Isothiocyanate, a Vegetable-Derived Compound, Induces Apoptosis via ROS Accumulation and DNA Damage in Canine Lymphoma and Leukemia Cells

Treatment of neoplastic diseases in companion animals is one of the most important problems of modern veterinary medicine. Given the growing interest in substances of natural origin as potential anti-cancer drugs, our goal was to examine the effectiveness of benzyl isothiocyanate (BITC), a compound...

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Main Authors: Marta Henklewska, Aleksandra Pawlak, Rong-Fang Li, Jine Yi, Iwona Zbyryt, Bożena Obmińska-Mrukowicz
Format: Article
Language:English
Published: MDPI AG 2021-10-01
Series:International Journal of Molecular Sciences
Subjects:
Online Access:https://www.mdpi.com/1422-0067/22/21/11772
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author Marta Henklewska
Aleksandra Pawlak
Rong-Fang Li
Jine Yi
Iwona Zbyryt
Bożena Obmińska-Mrukowicz
author_facet Marta Henklewska
Aleksandra Pawlak
Rong-Fang Li
Jine Yi
Iwona Zbyryt
Bożena Obmińska-Mrukowicz
author_sort Marta Henklewska
collection DOAJ
description Treatment of neoplastic diseases in companion animals is one of the most important problems of modern veterinary medicine. Given the growing interest in substances of natural origin as potential anti-cancer drugs, our goal was to examine the effectiveness of benzyl isothiocyanate (BITC), a compound found in cruciferous vegetables, against canine lymphoma and leukemia. These are the one of the most common canine cancer types, and chemotherapy is the only treatment option. The study involved established cell lines originating from various hematopoietic malignancies: CLBL-1, GL-1, CLB70 and CNK-89, immortalized noncancerous cell lines: MDCK and NIH-3T3 and canine peripheral blood mononuclear cells (PBMCs). The cytotoxic activity of BITC, apoptosis induction, caspase activity and ROS generation were evaluated by flow cytometry. H2AX phosphorylation was assessed by western blot. The study showed that the compound was especially active against B lymphocyte-derived malignant cells. Their death resulted from caspase-dependent apoptosis. BITC induced ROS accumulation, and glutathione precursor N-acetyl-l-cysteine reversed the effect of the compound, thus proving the role of oxidative stress in BITC activity. In addition, exposure to the compound induced DNA damage in the tested cells. This is the first study that provides information on the activity of BITC in canine hematopoietic malignancies and suggests that the compound may be particularly useful in B-cell neoplasms treatment.
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spelling doaj.art-04aa656ac79846899bcaf02fe3a6b8492023-11-22T20:57:38ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-10-0122211177210.3390/ijms222111772Benzyl Isothiocyanate, a Vegetable-Derived Compound, Induces Apoptosis via ROS Accumulation and DNA Damage in Canine Lymphoma and Leukemia CellsMarta Henklewska0Aleksandra Pawlak1Rong-Fang Li2Jine Yi3Iwona Zbyryt4Bożena Obmińska-Mrukowicz5Department of Pharmacology and Toxicology, Wrocław University of Environmental and Life Sciences, C.K. Norwida 31, 50-375 Wrocław, PolandDepartment of Pharmacology and Toxicology, Wrocław University of Environmental and Life Sciences, C.K. Norwida 31, 50-375 Wrocław, PolandHunan Engineering Research Center of Livestock and Poultry Health Care, Colleges of Veterinary Medicine, Hunan Agricultural University, Changsha 410128, ChinaHunan Engineering Research Center of Livestock and Poultry Health Care, Colleges of Veterinary Medicine, Hunan Agricultural University, Changsha 410128, ChinaDepartment of Epizootiology and Clinic of Birds and Exotic Animals, Wrocław University of Environmental and Life Sciences, C.K. Norwida 31, 50-375 Wrocław, PolandDepartment of Pharmacology and Toxicology, Wrocław University of Environmental and Life Sciences, C.K. Norwida 31, 50-375 Wrocław, PolandTreatment of neoplastic diseases in companion animals is one of the most important problems of modern veterinary medicine. Given the growing interest in substances of natural origin as potential anti-cancer drugs, our goal was to examine the effectiveness of benzyl isothiocyanate (BITC), a compound found in cruciferous vegetables, against canine lymphoma and leukemia. These are the one of the most common canine cancer types, and chemotherapy is the only treatment option. The study involved established cell lines originating from various hematopoietic malignancies: CLBL-1, GL-1, CLB70 and CNK-89, immortalized noncancerous cell lines: MDCK and NIH-3T3 and canine peripheral blood mononuclear cells (PBMCs). The cytotoxic activity of BITC, apoptosis induction, caspase activity and ROS generation were evaluated by flow cytometry. H2AX phosphorylation was assessed by western blot. The study showed that the compound was especially active against B lymphocyte-derived malignant cells. Their death resulted from caspase-dependent apoptosis. BITC induced ROS accumulation, and glutathione precursor N-acetyl-l-cysteine reversed the effect of the compound, thus proving the role of oxidative stress in BITC activity. In addition, exposure to the compound induced DNA damage in the tested cells. This is the first study that provides information on the activity of BITC in canine hematopoietic malignancies and suggests that the compound may be particularly useful in B-cell neoplasms treatment.https://www.mdpi.com/1422-0067/22/21/11772BITCanti-cancer drugscanine cancerscancer treatmentoxidative stress
spellingShingle Marta Henklewska
Aleksandra Pawlak
Rong-Fang Li
Jine Yi
Iwona Zbyryt
Bożena Obmińska-Mrukowicz
Benzyl Isothiocyanate, a Vegetable-Derived Compound, Induces Apoptosis via ROS Accumulation and DNA Damage in Canine Lymphoma and Leukemia Cells
International Journal of Molecular Sciences
BITC
anti-cancer drugs
canine cancers
cancer treatment
oxidative stress
title Benzyl Isothiocyanate, a Vegetable-Derived Compound, Induces Apoptosis via ROS Accumulation and DNA Damage in Canine Lymphoma and Leukemia Cells
title_full Benzyl Isothiocyanate, a Vegetable-Derived Compound, Induces Apoptosis via ROS Accumulation and DNA Damage in Canine Lymphoma and Leukemia Cells
title_fullStr Benzyl Isothiocyanate, a Vegetable-Derived Compound, Induces Apoptosis via ROS Accumulation and DNA Damage in Canine Lymphoma and Leukemia Cells
title_full_unstemmed Benzyl Isothiocyanate, a Vegetable-Derived Compound, Induces Apoptosis via ROS Accumulation and DNA Damage in Canine Lymphoma and Leukemia Cells
title_short Benzyl Isothiocyanate, a Vegetable-Derived Compound, Induces Apoptosis via ROS Accumulation and DNA Damage in Canine Lymphoma and Leukemia Cells
title_sort benzyl isothiocyanate a vegetable derived compound induces apoptosis via ros accumulation and dna damage in canine lymphoma and leukemia cells
topic BITC
anti-cancer drugs
canine cancers
cancer treatment
oxidative stress
url https://www.mdpi.com/1422-0067/22/21/11772
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