G2/M arrest and mitotic slippage induced by fenbendazole in canine melanoma cells
Abstract Background The use of fenbendazole (FBZ) in terminal cancer patients has recently increased, as anthelminthic drugs, such as FBZ and benzimidazole, exhibit anti‐tubulin effects in tumour cells. Objectives The present study evaluated the in vitro anti‐cancer effects of FBZ in five canine mel...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2022-05-01
|
| Series: | Veterinary Medicine and Science |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/vms3.733 |
| _version_ | 1797683423589957632 |
|---|---|
| author | Sehoon Kim Shashini Kanchanamala Perera Seo‐In Choi Robert B. Rebhun Kyoung‐won Seo |
| author_facet | Sehoon Kim Shashini Kanchanamala Perera Seo‐In Choi Robert B. Rebhun Kyoung‐won Seo |
| author_sort | Sehoon Kim |
| collection | DOAJ |
| description | Abstract Background The use of fenbendazole (FBZ) in terminal cancer patients has recently increased, as anthelminthic drugs, such as FBZ and benzimidazole, exhibit anti‐tubulin effects in tumour cells. Objectives The present study evaluated the in vitro anti‐cancer effects of FBZ in five canine melanoma cell lines originating from the oral cavity (UCDK9M3, UCDK9M4, UCDK9M5, KMeC and LMeC). Methods Five canine melanoma cell lines were treated with FBZ and analysed with cell viability assay, cell cycle analysis, western blot assay and immunofluorescence staining to identify apoptotic effect, cell cycle arrest, microtubule disruption and mitotic slippage. Results Cell viability was reduced in all melanoma cell lines in a dose‐dependent manner after FBZ treatment. Through cell cycle analysis, G2/M arrest and mitotic slippage were identified, which showed a time‐dependent change. All treatment concentrations induced increased cleaved PARP signals in western blot analysis compared to the control groups. Immunofluorescence of cells treated for 24 h revealed defects in microtubule structure, multinucleation or macronucleation. With the exception of UCDK9M3, the melanoma cells showed mitotic slippage and post‐slippage death, indicative of mitotic catastrophe. Conclusions These results indicate that FBZ exhibits anti‐cancer effects in vitro against canine melanoma cells; however, further in vivo studies regarding the clinical applications of FBZ are required. |
| first_indexed | 2024-03-12T00:15:05Z |
| format | Article |
| id | doaj.art-951bc0c7b05d4e67a9e7d6d541eb08a1 |
| institution | Directory Open Access Journal |
| issn | 2053-1095 |
| language | English |
| last_indexed | 2024-03-12T00:15:05Z |
| publishDate | 2022-05-01 |
| publisher | Wiley |
| record_format | Article |
| series | Veterinary Medicine and Science |
| spelling | doaj.art-951bc0c7b05d4e67a9e7d6d541eb08a12023-09-15T15:20:44ZengWileyVeterinary Medicine and Science2053-10952022-05-018396698110.1002/vms3.733G2/M arrest and mitotic slippage induced by fenbendazole in canine melanoma cellsSehoon Kim0Shashini Kanchanamala Perera1Seo‐In Choi2Robert B. Rebhun3Kyoung‐won Seo4Department of Veterinary Internal Medicine, College of Veterinary Medicine Chungnam National University Daejeon KoreaDepartment of Veterinary Internal Medicine, College of Veterinary Medicine Chungnam National University Daejeon KoreaDepartment of Veterinary Internal Medicine, College of Veterinary Medicine Chungnam National University Daejeon KoreaCenter for Companion Animal Health Department of Surgical and Radiological Sciences, School of Veterinary Medicine University of California Davis CaliforniaDepartment of Veterinary Internal Medicine, College of Veterinary Medicine Seoul National University Korea SeoulAbstract Background The use of fenbendazole (FBZ) in terminal cancer patients has recently increased, as anthelminthic drugs, such as FBZ and benzimidazole, exhibit anti‐tubulin effects in tumour cells. Objectives The present study evaluated the in vitro anti‐cancer effects of FBZ in five canine melanoma cell lines originating from the oral cavity (UCDK9M3, UCDK9M4, UCDK9M5, KMeC and LMeC). Methods Five canine melanoma cell lines were treated with FBZ and analysed with cell viability assay, cell cycle analysis, western blot assay and immunofluorescence staining to identify apoptotic effect, cell cycle arrest, microtubule disruption and mitotic slippage. Results Cell viability was reduced in all melanoma cell lines in a dose‐dependent manner after FBZ treatment. Through cell cycle analysis, G2/M arrest and mitotic slippage were identified, which showed a time‐dependent change. All treatment concentrations induced increased cleaved PARP signals in western blot analysis compared to the control groups. Immunofluorescence of cells treated for 24 h revealed defects in microtubule structure, multinucleation or macronucleation. With the exception of UCDK9M3, the melanoma cells showed mitotic slippage and post‐slippage death, indicative of mitotic catastrophe. Conclusions These results indicate that FBZ exhibits anti‐cancer effects in vitro against canine melanoma cells; however, further in vivo studies regarding the clinical applications of FBZ are required.https://doi.org/10.1002/vms3.733anti‐tumour effectapoptosiscanine melanoma cellfenbendazoleG2/M cell cycle arrestmitotic slippage |
| spellingShingle | Sehoon Kim Shashini Kanchanamala Perera Seo‐In Choi Robert B. Rebhun Kyoung‐won Seo G2/M arrest and mitotic slippage induced by fenbendazole in canine melanoma cells Veterinary Medicine and Science anti‐tumour effect apoptosis canine melanoma cell fenbendazole G2/M cell cycle arrest mitotic slippage |
| title | G2/M arrest and mitotic slippage induced by fenbendazole in canine melanoma cells |
| title_full | G2/M arrest and mitotic slippage induced by fenbendazole in canine melanoma cells |
| title_fullStr | G2/M arrest and mitotic slippage induced by fenbendazole in canine melanoma cells |
| title_full_unstemmed | G2/M arrest and mitotic slippage induced by fenbendazole in canine melanoma cells |
| title_short | G2/M arrest and mitotic slippage induced by fenbendazole in canine melanoma cells |
| title_sort | g2 m arrest and mitotic slippage induced by fenbendazole in canine melanoma cells |
| topic | anti‐tumour effect apoptosis canine melanoma cell fenbendazole G2/M cell cycle arrest mitotic slippage |
| url | https://doi.org/10.1002/vms3.733 |
| work_keys_str_mv | AT sehoonkim g2marrestandmitoticslippageinducedbyfenbendazoleincaninemelanomacells AT shashinikanchanamalaperera g2marrestandmitoticslippageinducedbyfenbendazoleincaninemelanomacells AT seoinchoi g2marrestandmitoticslippageinducedbyfenbendazoleincaninemelanomacells AT robertbrebhun g2marrestandmitoticslippageinducedbyfenbendazoleincaninemelanomacells AT kyoungwonseo g2marrestandmitoticslippageinducedbyfenbendazoleincaninemelanomacells |