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

Int J Mol Sci. 2021 Oct 29;22(21):11772. doi: 10.3390/ijms222111772.

Abstract

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.

Keywords: BITC; anti-cancer drugs; cancer treatment; canine cancers; oxidative stress.

MeSH terms

  • Animals
  • Antineoplastic Agents, Phytogenic / chemistry
  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Apoptosis / drug effects
  • Cell Line, Tumor
  • DNA Damage / drug effects
  • Dog Diseases / drug therapy*
  • Dog Diseases / genetics
  • Dog Diseases / metabolism
  • Dogs / genetics
  • Dogs / metabolism
  • Isothiocyanates / chemistry
  • Isothiocyanates / pharmacology*
  • Leukemia / drug therapy
  • Leukemia / genetics
  • Leukemia / metabolism
  • Leukemia / veterinary*
  • Lymphoma / drug therapy
  • Lymphoma / genetics
  • Lymphoma / metabolism
  • Lymphoma / veterinary*
  • Madin Darby Canine Kidney Cells
  • Mice
  • NIH 3T3 Cells
  • Reactive Oxygen Species / metabolism
  • Vegetables / chemistry

Substances

  • Antineoplastic Agents, Phytogenic
  • Isothiocyanates
  • Reactive Oxygen Species
  • benzyl isothiocyanate