A newly established canine NK‐type cell line and its cytotoxic properties

Grudzień, Małgorzata; Pawlak, Aleksandra; Kutkowska, Justyna; Zioło, Ewa; Wysokińska, Edyta; Hildebrand, W.; Obmińska-Mrukowicz, Bożena; Strządała, Leon; Rapak, Andrzej

doi:10.1111/vco.12695

Cited by 9 publications

(14 citation statements)

References 31 publications

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“…A structural isomer of lactone 3, namely 2 -methoxy derivative 2, showed lower cytotoxic potency, as illustrated in Table 1 by IC 50 values for each derivative. Both compounds were more effective towards CLBL-1 and CLB70 cell lines (representing B-cell lymphoma and chronic type B leukemia, respectively) [21,22] than towards the rarer and more difficultto-treat types of hematopoietic cancer in dogs-acute leukemia of not clearly defined phenotype (B/T) [22,23], or NK cell lymphoma [24]. The remaining tests confirmed that the difference between these isomers concerns only the strength of their action and not the way in which they kill cancer cells.…”

Section: Discussionmentioning

confidence: 98%

“…The study involved a panel of canine cancer cell lines: CLBL-1 (B-cell lymphoma), GL-1 (B/T-cell leukemia), CLB70 (B-cell chronic lymphocytic leukemia) and CNK-89 (NK-cell lymphoma), and a normal canine cell line (MDCK). CLBL-1 was obtained from Barbara C. Ruetgen from the Institute of Immunology, Department of Pathobiology, University of Veterinary Medicine, Vienna, Austria [22]; GL-1 from Yasuhito Fujino and Hajime Tsujimoto of the University of Tokyo, Department of Veterinary Internal Medicine [23]; while CLB70 [21] and CNK-89 [24] were established in our laboratory. The MDCK cell line was purchased from Sigma Aldrich (Steinheim, Germany).…”

Section: Cell Lines and Cell Culturementioning

confidence: 99%

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Methoxy-Substituted γ-Oxa-ε-Lactones Derived from Flavanones—Comparison of Their Anti-Tumor Activity In Vitro

et al. 2021

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Background: The study investigated four flavanone-derived γ-oxa-ε-lactones: a parent unsubstituted compound and its three derivatives with the methoxy group in positions 2′, 4′ and 8. Our objective was to find out if the introduction of the methoxy group into the aromatic ring affects in vitro anti-tumor potency of the investigated lactones. Methods: Cytotoxic and pro-apoptotic effects were assessed with cytometric tests with propidium iodide, annexin V, and Western blot techniques. We also investigated potential synergistic potency of the tested lactones and glucocorticoids in canine lymphoma/leukemia cell lines. Results: The tested flavanone-derived lactones showed anti-cancer activity in vitro. Depending on its location, the methoxy group either increased or decreased cytotoxicity of the derivatives as compared with the parent compound. The most potent lactone was the one with the methoxy group at position 4′ of the B ring (compound 3), and the weakest activity was observed when the group was located at C-8 in the A ring. A combination of the lactones with glucocorticoids confirmed their synergy in anti-tumor activity in vitro. Conclusions: Methoxy-substituted flavanone-derived lactones effectively kill canine lymphoma/leukemia cells in vitro and, thanks to their synergistic action with glucocorticoids, may potentially be applied in the treatment of hematopoietic cancers.

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Section: Discussionmentioning

confidence: 98%

Section: Cell Lines and Cell Culturementioning

confidence: 99%

Methoxy-Substituted γ-Oxa-ε-Lactones Derived from Flavanones—Comparison of Their Anti-Tumor Activity In Vitro

et al. 2021

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“…The increasing availability of a wide panel of various canine cancer cell lines hugely facilitates such studies. [66][67][68][69] Due to significance of DDR disorders in the cancer development in dogs, this review discusses the key components of the DDR, presents their physiological role and the abnormalities associated with these proteins found in canine cancers. We consider findings on the potential causes of genetic instability in canine cancers and indicate potential new research directions.…”

Section: Dna Damage Response In Canine Cancersmentioning

confidence: 99%

“…The increasing availability of a wide panel of various canine cancer cell lines hugely facilitates such studies. 66 , 67 , 68 , 69 …”

Section: Introductionmentioning

confidence: 99%

DNA damage response proteins in canine cancer as potential research targets in comparative oncology

Hernandez-Suarez

Gillespie

Pawlak

2022

Vet Comparative Oncology

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The DNA damage response (DDR) is a complex signal transduction network that is activated when endogenous or exogenous genotoxins damage or interfere with the replication of genomic DNA. Under such conditions, the DDR promotes DNA repair and ensures accurate replication and division of the genome. High levels of genomic instability are frequently observed in cancers and can stem from germline loss‐of‐function mutations in certain DDR genes, such as BRCA1, BRCA2, and p53, that form the basis of human cancer predisposition syndromes. In addition, mutation and/or aberrant expression of multiple DDR genes are frequently observed in sporadic human cancers. As a result, the DDR is considered to represent a viable target for cancer therapy in humans and a variety of strategies are under investigation. Cancer is also a significant cause of mortality in dogs, a species that offers certain advantages for experimental oncology. Domestic dogs present numerous inbred lines, many of which display predisposition to specific forms of cancer and the study of which may provide insight into the biological basis of this susceptibility. In addition, clinical trials are possible in dogs and may lead to therapeutic insights that could ultimately be extended to humans. Here we review what is known specifically about the DDR in dogs and discuss how this knowledge could be extended and exploited to advance experimental oncology in this species.

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“…GL-1 [60] was provided by Yasuhito Fujino and Hajime Tsujimoto from the University of Tokyo, Department of Veterinary Internal Medicine. CLB70 [61] and CNK-89 [62] were established in our laboratory.…”

Section: Cell Lines and Cell Culturementioning

confidence: 99%

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

Henklewska

Pawlak

et al. 2021

IJMS

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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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A newly established canine NK‐type cell line and its cytotoxic properties

Cited by 9 publications

References 31 publications

Methoxy-Substituted γ-Oxa-ε-Lactones Derived from Flavanones—Comparison of Their Anti-Tumor Activity In Vitro

Methoxy-Substituted γ-Oxa-ε-Lactones Derived from Flavanones—Comparison of Their Anti-Tumor Activity In Vitro

DNA damage response proteins in canine cancer as potential research targets in comparative oncology

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

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