The second-generation curcumin analogue RL71 elicits G2/M cell cycle arrest and apoptosis in canine osteosarcoma cells.

IF 2.3 2区 农林科学 Q1 VETERINARY SCIENCES Veterinary and comparative oncology Pub Date : 2023-12-01 Epub Date: 2023-07-12 DOI:10.1111/vco.12922
Barnaby Kelly, Douglas Thamm, Rhonda J Rosengren
{"title":"The second-generation curcumin analogue RL71 elicits G2/M cell cycle arrest and apoptosis in canine osteosarcoma cells.","authors":"Barnaby Kelly, Douglas Thamm, Rhonda J Rosengren","doi":"10.1111/vco.12922","DOIUrl":null,"url":null,"abstract":"<p><p>Canine osteosarcoma is an aggressive cancer, comprising 85% of canine bone neoplasms. Current treatment practices of surgery and chemotherapy increase 1-year survival by only 45%. The curcumin analogue RL71, has demonstrated potent in vitro and in vivo efficacy in several models of human breast cancer through increased apoptosis and cell cycle arrest. Thus, the present study aimed to investigate efficacy of curcumin analogues in two canine osteosarcoma cell lines. Osteosarcoma cell viability was assessed using the sulforhodamine B assay and mechanisms of action were determined by analysing the levels of cell cycle and apoptotic regulatory proteins via Western blotting. Further evidence was obtained using flow cytometry to detect cell cycle distribution and the number of apoptotic cells. RL71 was the most potent curcumin analogue with EC<sub>50</sub> values of 0.64 ± 0.04 and 0.38 ± 0.009 μM (n = 3) in D-17 (commercial) and Gracie canine osteosarcoma cells, respectively. RL71 significantly increased the ratio of cleaved-caspase 3 to pro-caspase 3 and the level of apoptotic cells at the 2× and 5× EC<sub>50</sub> concentration (p < 0.001, n = 3). Furthermore, at the same concentration, RL71 significantly increased the number of cells in the G2/M phase. In conclusion, RL71 has potent cytotoxic activity in canine osteosarcoma cells triggering G2/M arrest and apoptosis at concentrations achievable in vivo. Future research should further investigate molecular mechanisms for these changes in other canine osteosarcoma cell lines prior to in vivo investigation.</p>","PeriodicalId":23693,"journal":{"name":"Veterinary and comparative oncology","volume":" ","pages":"595-604"},"PeriodicalIF":2.3000,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Veterinary and comparative oncology","FirstCategoryId":"97","ListUrlMain":"https://doi.org/10.1111/vco.12922","RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2023/7/12 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"VETERINARY SCIENCES","Score":null,"Total":0}
引用次数: 0

Abstract

Canine osteosarcoma is an aggressive cancer, comprising 85% of canine bone neoplasms. Current treatment practices of surgery and chemotherapy increase 1-year survival by only 45%. The curcumin analogue RL71, has demonstrated potent in vitro and in vivo efficacy in several models of human breast cancer through increased apoptosis and cell cycle arrest. Thus, the present study aimed to investigate efficacy of curcumin analogues in two canine osteosarcoma cell lines. Osteosarcoma cell viability was assessed using the sulforhodamine B assay and mechanisms of action were determined by analysing the levels of cell cycle and apoptotic regulatory proteins via Western blotting. Further evidence was obtained using flow cytometry to detect cell cycle distribution and the number of apoptotic cells. RL71 was the most potent curcumin analogue with EC50 values of 0.64 ± 0.04 and 0.38 ± 0.009 μM (n = 3) in D-17 (commercial) and Gracie canine osteosarcoma cells, respectively. RL71 significantly increased the ratio of cleaved-caspase 3 to pro-caspase 3 and the level of apoptotic cells at the 2× and 5× EC50 concentration (p < 0.001, n = 3). Furthermore, at the same concentration, RL71 significantly increased the number of cells in the G2/M phase. In conclusion, RL71 has potent cytotoxic activity in canine osteosarcoma cells triggering G2/M arrest and apoptosis at concentrations achievable in vivo. Future research should further investigate molecular mechanisms for these changes in other canine osteosarcoma cell lines prior to in vivo investigation.

查看原文
分享 分享
微信好友 朋友圈 QQ好友 复制链接
本刊更多论文
第二代姜黄素类似物RL71诱导犬骨肉瘤细胞G2/M细胞周期阻滞和凋亡。
犬骨肉瘤是一种侵袭性癌症,占犬骨肿瘤的85%。目前手术和化疗的治疗方法只增加了45%的1年生存率。姜黄素类似物RL71在体外和体内通过增加细胞凋亡和细胞周期阻滞在几种人类乳腺癌模型中显示出强大的功效。因此,本研究旨在探讨姜黄素类似物对两种犬骨肉瘤细胞系的作用。使用硫代丹B法评估骨肉瘤细胞活力,并通过Western blotting分析细胞周期和凋亡调节蛋白的水平来确定作用机制。利用流式细胞术检测细胞周期分布和凋亡细胞数量,获得进一步证据。RL71是最有效的姜黄素类似物,在D-17(商业)和Gracie犬骨肉瘤细胞中的EC50值分别为0.64±0.04和0.38±0.009 μM (n = 3)。RL71显著提高了2倍和5倍EC50浓度下caspase - 3与caspase - 3的比值及凋亡细胞的水平(p
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 去求助
来源期刊
Veterinary and comparative oncology
Veterinary and comparative oncology 农林科学-兽医学
CiteScore
4.80
自引率
9.50%
发文量
75
审稿时长
>24 weeks
期刊介绍: Veterinary and Comparative Oncology (VCO) is an international, peer-reviewed journal integrating clinical and scientific information from a variety of related disciplines and from worldwide sources for all veterinary oncologists and cancer researchers concerned with aetiology, diagnosis and clinical course of cancer in domestic animals and its prevention. With the ultimate aim of diminishing suffering from cancer, the journal supports the transfer of knowledge in all aspects of veterinary oncology, from the application of new laboratory technology to cancer prevention, early detection, diagnosis and therapy. In addition to original articles, the journal publishes solicited editorials, review articles, commentary, correspondence and abstracts from the published literature. Accordingly, studies describing laboratory work performed exclusively in purpose-bred domestic animals (e.g. dogs, cats, horses) will not be considered.
期刊最新文献
Blood Neutrophil-to-Lymphocyte Ratio as a Potential Prognostic Marker in Dogs ≤10 kg With Multicentric Lymphoma. Incorporation of Biologic Variables Into the Staging for Canine Cutaneous and Subcutaneous Mast Cell Tumours: Proposal of the UBo pTNM System. Overactivation of Signal Transducer and Activator of Transcription 3 in Canine Hepatocellular Carcinoma and Its Prognostic Significance. Evaluation of the Amount of Compounded Chemotherapy Drugs: A Comparison Between Nine Compounding Pharmacies. Macrophage Colony Stimulating Factor (M-CSF) and Interleukin-34 (IL-34) Expression in Canine Osteosarcoma in the Context of the Tumour Immune Microenvironment.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
已复制链接
已复制链接
快去分享给好友吧!
我知道了
×
扫码分享
扫码分享
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1