PGV-1 导致纺锤体微管组织混乱,导致 HLF 和 HuH6 细胞有丝分裂异常,并与 MYCN 状态改变有关。

IF 3.1 Q2 PHARMACOLOGY & PHARMACY Advanced pharmaceutical bulletin Pub Date : 2024-10-01 Epub Date: 2024-07-31 DOI:10.34172/apb.2024.058
Nadzifa Nugraheni, Ummi Maryam Zulfin, Beni Lestari, Novia Permata Hapsari, Muthi Ikawati, Rohmad Yudi Utomo, Yusuke Suenaga, Yoshitaka Hippo, Edy Meiyanto
{"title":"PGV-1 导致纺锤体微管组织混乱,导致 HLF 和 HuH6 细胞有丝分裂异常,并与 MYCN 状态改变有关。","authors":"Nadzifa Nugraheni, Ummi Maryam Zulfin, Beni Lestari, Novia Permata Hapsari, Muthi Ikawati, Rohmad Yudi Utomo, Yusuke Suenaga, Yoshitaka Hippo, Edy Meiyanto","doi":"10.34172/apb.2024.058","DOIUrl":null,"url":null,"abstract":"<p><strong>Purpose: </strong>The HLF and HuH-6 cell lines represent hepatocellular carcinoma (HCC) with different characteristics in chromosome content that may give different drug responses. Here, PGV-1 was intended to challenge the growth-suppressing effect on HLF and HuH-6 and trace the molecular target mechanism of action compared to sorafenib.</p><p><strong>Methods: </strong>We applied MTT cytotoxic assay, colony forming assay, flow cytometry analysis, immunofluorescence assay and western blot assay.</p><p><strong>Results: </strong>PGV-1 exhibited cytotoxic effects on HLF and HuH-6 with IC-50 values of 1 µM and 2 µM, respectively, whereas sorafenib showed less cytotoxicity with IC-50 values of 5 µM and 8 µM respectively. PGV-1 suppressed the cell growth permanently but not for sorafenib. Sorafenib did not change the cell cycle profiles on both cells, but PGV-1 arrested the cells at G2/M with the characteristic of senescent cells and mitotic disarrangement. PGV-1 and sorafenib showed the same effect in downregulating p-EGFR, indicating that both compounds have the same target on EGFR activation or as Tyrosine kinase inhibitors. PGV-1 suppressed the MYCN expression in HuH-6 and HLF cells but stabilized cMYC-T58 indicating that even though the MYCN was downregulated, the cells maintained the active form of cMYC. In this regard, PGV-1 also stabilized the expression of PLK-1 and AurA.</p><p><strong>Conclusion: </strong>PGV-1 elicits stronger cytotoxic properties compared to sorafenib. The lower the MYCN expression, the higher the cytotoxic effect of PGV-1. PGV-1 abrogates cell cycle progression of both cells in mitosis through EGFR inhibition and stabilizes PLK-1 and AurA in correlation with the suppression of MYCN expression.</p>","PeriodicalId":7256,"journal":{"name":"Advanced pharmaceutical bulletin","volume":"14 3","pages":"665-674"},"PeriodicalIF":3.1000,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11530888/pdf/","citationCount":"0","resultStr":"{\"title\":\"PGV-1 Causes Disarrangement of Spindle Microtubule Organization Resulting in Aberrant Mitosis in HLF and HuH6 Cells Associated with Altered MYCN Status.\",\"authors\":\"Nadzifa Nugraheni, Ummi Maryam Zulfin, Beni Lestari, Novia Permata Hapsari, Muthi Ikawati, Rohmad Yudi Utomo, Yusuke Suenaga, Yoshitaka Hippo, Edy Meiyanto\",\"doi\":\"10.34172/apb.2024.058\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Purpose: </strong>The HLF and HuH-6 cell lines represent hepatocellular carcinoma (HCC) with different characteristics in chromosome content that may give different drug responses. Here, PGV-1 was intended to challenge the growth-suppressing effect on HLF and HuH-6 and trace the molecular target mechanism of action compared to sorafenib.</p><p><strong>Methods: </strong>We applied MTT cytotoxic assay, colony forming assay, flow cytometry analysis, immunofluorescence assay and western blot assay.</p><p><strong>Results: </strong>PGV-1 exhibited cytotoxic effects on HLF and HuH-6 with IC-50 values of 1 µM and 2 µM, respectively, whereas sorafenib showed less cytotoxicity with IC-50 values of 5 µM and 8 µM respectively. PGV-1 suppressed the cell growth permanently but not for sorafenib. Sorafenib did not change the cell cycle profiles on both cells, but PGV-1 arrested the cells at G2/M with the characteristic of senescent cells and mitotic disarrangement. PGV-1 and sorafenib showed the same effect in downregulating p-EGFR, indicating that both compounds have the same target on EGFR activation or as Tyrosine kinase inhibitors. PGV-1 suppressed the MYCN expression in HuH-6 and HLF cells but stabilized cMYC-T58 indicating that even though the MYCN was downregulated, the cells maintained the active form of cMYC. In this regard, PGV-1 also stabilized the expression of PLK-1 and AurA.</p><p><strong>Conclusion: </strong>PGV-1 elicits stronger cytotoxic properties compared to sorafenib. The lower the MYCN expression, the higher the cytotoxic effect of PGV-1. PGV-1 abrogates cell cycle progression of both cells in mitosis through EGFR inhibition and stabilizes PLK-1 and AurA in correlation with the suppression of MYCN expression.</p>\",\"PeriodicalId\":7256,\"journal\":{\"name\":\"Advanced pharmaceutical bulletin\",\"volume\":\"14 3\",\"pages\":\"665-674\"},\"PeriodicalIF\":3.1000,\"publicationDate\":\"2024-10-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11530888/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Advanced pharmaceutical bulletin\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.34172/apb.2024.058\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/7/31 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q2\",\"JCRName\":\"PHARMACOLOGY & PHARMACY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Advanced pharmaceutical bulletin","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.34172/apb.2024.058","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/7/31 0:00:00","PubModel":"Epub","JCR":"Q2","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
引用次数: 0

摘要

目的:HLF和HuH-6细胞系代表肝细胞癌(HCC),其染色体含量的不同可能导致不同的药物反应。在此,PGV-1 试图挑战其对 HLF 和 HuH-6 的生长抑制作用,并追踪其与索拉非尼相比的分子靶点作用机制:方法:采用MTT细胞毒性试验、集落形成试验、流式细胞术分析、免疫荧光试验和Western blot试验:结果:PGV-1 对 HLF 和 HuH-6 具有细胞毒性作用,IC-50 值分别为 1 µM 和 2 µM,而索拉非尼的细胞毒性较弱,IC-50 值分别为 5 µM 和 8 µM。PGV-1 能永久抑制细胞生长,而索拉非尼则不能。索拉非尼没有改变两种细胞的细胞周期图谱,但 PGV-1 使细胞停滞在 G2/M,具有衰老细胞和有丝分裂紊乱的特征。PGV-1 和索拉非尼在下调 p-EGFR 方面表现出相同的效果,这表明这两种化合物在表皮生长因子受体活化或作为酪氨酸激酶抑制剂方面具有相同的靶点。PGV-1抑制了HuH-6和HLF细胞中MYCN的表达,但稳定了cMYC-T58,这表明即使MYCN被下调,细胞仍保持着cMYC的活性形式。在这方面,PGV-1 还能稳定 PLK-1 和 AurA 的表达:结论:与索拉非尼相比,PGV-1具有更强的细胞毒性。结论:与索拉非尼相比,PGV-1具有更强的细胞毒性,MYCN表达越低,PGV-1的细胞毒性作用越强。通过抑制表皮生长因子受体,PGV-1可抑制两种细胞在有丝分裂期的细胞周期进展,并稳定PLK-1和AurA,这与抑制MYCN表达有关。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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
PGV-1 Causes Disarrangement of Spindle Microtubule Organization Resulting in Aberrant Mitosis in HLF and HuH6 Cells Associated with Altered MYCN Status.

Purpose: The HLF and HuH-6 cell lines represent hepatocellular carcinoma (HCC) with different characteristics in chromosome content that may give different drug responses. Here, PGV-1 was intended to challenge the growth-suppressing effect on HLF and HuH-6 and trace the molecular target mechanism of action compared to sorafenib.

Methods: We applied MTT cytotoxic assay, colony forming assay, flow cytometry analysis, immunofluorescence assay and western blot assay.

Results: PGV-1 exhibited cytotoxic effects on HLF and HuH-6 with IC-50 values of 1 µM and 2 µM, respectively, whereas sorafenib showed less cytotoxicity with IC-50 values of 5 µM and 8 µM respectively. PGV-1 suppressed the cell growth permanently but not for sorafenib. Sorafenib did not change the cell cycle profiles on both cells, but PGV-1 arrested the cells at G2/M with the characteristic of senescent cells and mitotic disarrangement. PGV-1 and sorafenib showed the same effect in downregulating p-EGFR, indicating that both compounds have the same target on EGFR activation or as Tyrosine kinase inhibitors. PGV-1 suppressed the MYCN expression in HuH-6 and HLF cells but stabilized cMYC-T58 indicating that even though the MYCN was downregulated, the cells maintained the active form of cMYC. In this regard, PGV-1 also stabilized the expression of PLK-1 and AurA.

Conclusion: PGV-1 elicits stronger cytotoxic properties compared to sorafenib. The lower the MYCN expression, the higher the cytotoxic effect of PGV-1. PGV-1 abrogates cell cycle progression of both cells in mitosis through EGFR inhibition and stabilizes PLK-1 and AurA in correlation with the suppression of MYCN expression.

求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
Advanced pharmaceutical bulletin
Advanced pharmaceutical bulletin PHARMACOLOGY & PHARMACY-
CiteScore
6.80
自引率
2.80%
发文量
51
审稿时长
12 weeks
期刊最新文献
Exploring the Interplay between the Warburg Effect and Glucolipotoxicity in Cancer Development: A Novel Perspective on Cancer Etiology. Cytobiological Alterations Induced by Celecoxib as an Anticancer Agent for Breast and Metastatic Breast Cancer. Development of Gentamicin Bilosomes Laden In Situ Gel for Topical Ocular Delivery: Optimization, In Vitro Characterization, Toxicity, and Anti-microbial Evaluation. Dual-stage Acting Dendrimeric Nanoparticle for Deepened Chemotherapeutic Drug Delivery to Tumor Cells. Evaluating the Accuracy of Large Language Model (ChatGPT) in Providing Information on Metastatic Breast Cancer.
×
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