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.
Highlights
As in humans, cancer in companion animals is nowadays regarded one of the most important chronic diseases, significantly impacting the quality of life and leading to its shortening [1]
The highest concentration used in the study (20 μM) was more potent toward all canine cancer cell lines than toward peripheral blood mononuclear cells (PBMCs) (p < 0.05) (Figure 2 and Table S2)
The cells derived from B lymphocytes, were sensitive, as their viability was significantly reduced by benzyl isothiocyanate (BITC) at a concentration representing only minor toxicity toward normal cells
Summary
Cancer in companion animals is nowadays regarded one of the most important chronic diseases, significantly impacting the quality of life and leading to its shortening [1]. What is the most important from the point of view of their use as potential anti-cancer drugs, they exhibit direct cytotoxic and proapoptotic activity against cancer cells, including those originating from the hematopoietic system [15,16,17,18]. The mechanism of their action is not fully clarified, it is known that ITCs as electrophiles react with nucleophiles, especially those with thiol residues. ITCs were shown to promote phosphorylation of stress-activated kinases such as JNK, p38, ERK 1/2 and to induce caspase dependent apoptosis [22,23]
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