AbstractCompounds that can induce oxidative stress in cancer cells while remaining nontoxic to healthy cells are extremely promising for potential anticancer drugs. 2,2′:6′,2′′-terpyridine-metal complexes possess these properties. The high level of activity (IC50 = 0.605 µM) of 2,2′:6′,2′′-terpyridine-metal complexes on lung, breast, pancreatic, and glioblastoma multiforme cancer lines and their selectivity (SI > 41.32) on human normal fibroblasts were confirmed and presented in this paper.

摘要可以在癌细胞中诱导氧化应激同时对健康细胞无毒的化合物对于潜在的抗癌药物是非常有希望的。2,2':6'，2''-三联吡啶金属配合物具有这些性质。本文证实并介绍了2,2':6'，2'-三联吡啶金属配合物对肺，乳腺，胰腺和胶质母细胞瘤多形性癌细胞系的高活性（IC50）=0.605µM）及其对人正常成纤维细胞的选择性（SI>41.32）。

The mechanism of action of these compounds is associated with the generation of reactive oxygen species, which affects several cellular pathways and signals. The results demonstrate that 2,2′:6′,2′′-terpyridine-metal complexes affect cell cycle inhibition in the G0/G1 phase as well as the activation of apoptosis and autophagy cell death.

这些化合物的作用机制与活性氧的产生有关，活性氧会影响几种细胞途径和信号。结果表明，2,2':6'，2''-三联吡啶金属配合物影响G0/G1期的细胞周期抑制以及细胞凋亡和自噬细胞死亡的激活。

These results were confirmed in several independent studies, including experiments measuring the fluorescence levels of reactive oxygen species, flow cytometry, and gene and protein analysis..

这些结果在几项独立研究中得到证实，包括测量活性氧荧光水平的实验，流式细胞术以及基因和蛋白质分析。。

IntroductionAccording to a Lancet Oncology study and others, a correlation was found between the human development index (HDI) and the occurrence of higher rates of lung, pancreatic, and breast cancers1,2. HDI is a combined index of a country’s level of human development, which is based on factors such as life expectancy, education, and income.

引言根据《柳叶刀》肿瘤学研究和其他研究，人类发展指数（HDI）与肺癌，胰腺癌和乳腺癌发生率较高之间存在相关性1,2。人类发展指数是一个国家人类发展水平的综合指数，它基于预期寿命、教育和收入等因素。

That being said, studies have shown that there is a significant correlation between HDI, cancer incidence, cancer type, and mortality rates. In recent years, breast cancer has been the most frequently diagnosed cancer worldwide, overtaking lung cancer. In particular, this type of cancer is a common problem among women living in developing countries and causes 11.7 million new cases annually.

尽管如此，研究表明，人类发展指数、癌症发病率、癌症类型和死亡率之间存在显著相关性。近年来，乳腺癌已超过肺癌成为全球最常被诊断出的癌症。特别是，这种类型的癌症是发展中国家女性的常见问题，每年导致1170万例新病例。

Lung cancer, on the other hand, has the highest mortality rate, which is steadily rising. The percentage of lung cancer deaths without gender distribution is about 18% of all cancer deaths3. The aforementioned types of cancer, as well as colorectum and prostate cancers, accounted for 50% of all diagnosed cancer types.

另一方面，肺癌死亡率最高，并在稳步上升。没有性别分布的肺癌死亡率约占所有癌症死亡率的18%3。上述类型的癌症以及结直肠癌和前列腺癌占所有诊断癌症类型的50%。

Glioblastoma (GBM), on the other hand, is not as common, but its course is often rapid and does not have a good prognosis. Statistical data show that 75% of GBM patients die within two years of diagnosis after undergoing intensive treatment regimens, and only about 5% survive five years. The median overall survival (mOS) for GBM patients remains at approximately 10.2 months4,5.

另一方面，胶质母细胞瘤（GBM）并不常见，但其病程通常很快，预后不佳。统计数据显示，75%的GBM患者在接受强化治疗方案后在诊断后两年内死亡，只有约5%的患者存活五年。GBM患者的中位总生存期（mOS）保持在大约10.2个月4,5。

Another very aggressive tumor type is pancreatic cancer, which owes its poor prognosis largely to a late diagnosis when an appropriate treatment regimen and resection cannot be implemented, as well as its high asymptomatic rates in the early stages6. Therefore, we chose to explore those four types of cancer, which are prevalent in Western societies, and w.

另一种非常侵袭性的肿瘤类型是胰腺癌，其预后不良主要是由于无法实施适当的治疗方案和切除术时的晚期诊断，以及早期无症状率高6。因此，我们选择探索西方社会普遍存在的这四种癌症，而w。

Data availability

数据可用性

Raw data are available upon request from the reviewer. Contact person - Anna Mrozek-Wilczkiewicz (anna.mrozek-wilczkiewicz@us.edu.pl).

原始数据可根据审稿人的要求提供。联系人-Anna Mrozek Wilczkiewicz(anna.mrozek-wilczkiewicz@us.edu.pl)。

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Download referencesAcknowledgementsThe study was supported by National Science Centre grants 2019/35/B/NZ5/04208 (KM) and 2020/39/O/NZ5/02342 (AMW, PZ). We thank our colleague Dr. Maciej Serda for his help in analyzing the MS spectra.Author informationAuthors and AffiliationsDepartment of Systems Biology and Engineering, Silesian University of Technology, Akademicka 2A, Gliwice, 44-100, PolandKatarzyna Malarz & Anna Mrozek-WilczkiewiczA.

下载参考文献致谢该研究得到了国家科学中心拨款2019/35/B/NZ5/04208（KM）和2020/39/O/NZ5/02342（AMW，PZ）的支持。我们感谢我们的同事Maciej Serda博士在分析MS光谱方面的帮助。作者信息作者和附属机构西里西亚理工大学系统生物学与工程系，Akademicka 2A，Gliwice，44-100，PolandKatarzyna Malarz＆Anna Mrozek WilczkiewiczA。

Chełkowski Institute of Physics, University of Silesia in Katowice, 75 Pułku Piechoty 1a, Chorzów, 41- 500, PolandKatarzyna Malarz, Patryk Ziola, Patryk Rurka & Anna Mrozek-WilczkiewiczFaculty of Chemistry, University of Opole, Oleska 48, Opole, 45-052, PolandDawid ZychAuthorsKatarzyna MalarzView author publicationsYou can also search for this author in.

卡托维兹西里西亚大学Chełkowski物理研究所，75 Pułku Piechoty 1a，Chorzow，41-500，PolandKatarzyna Malarz，Patryk Ziola，Patryk-Rurka，Anna Mrozek Wilczkiewicz奥波莱大学化学学院，Oleska 48，Opole，45-052，PolandDawid Zych作者Katarzyna-Malarz查看作者出版物您也可以在中搜索这位作者。

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PubMed Google ScholarDawid ZychView author publicationsYou can also search for this author in

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PubMed Google ScholarContributionsKM designed experiments, performed cytotoxicity, cell cycle, analysed data and wrote the manuscript; PZ performed cytotoxicity with metal ions, apoptosis, and immunoblotting assays; DZ planned and performed the chemical syntheses; PR conducted ROS, cytotoxicity with the antioxidant and qRT-PCR assays; AMW created research hypothesis, discussed the results and wrote the manuscript.

PubMed谷歌学术贡献SKM设计实验，进行细胞毒性，细胞周期，分析数据并撰写手稿；PZ用金属离子，细胞凋亡和免疫印迹分析进行细胞毒性；DZ计划并进行了化学合成；PR通过抗氧化剂和qRT-PCR测定进行ROS，细胞毒性；AMW创建了研究假设，讨论了结果并撰写了手稿。

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Reprints and permissionsAbout this articleCite this articleMalarz, K., Ziola, P., Zych, D. et al. Imbalance of redox homeostasis and altered cellular signaling induced by the metal complexes of terpyridine.

转载和许可本文引用本文Malarz，K.，Ziola，P.，Zych，D。等人。三联吡啶金属配合物诱导的氧化还原稳态失衡和细胞信号改变。

Sci Rep 14, 26951 (2024). https://doi.org/10.1038/s41598-024-77575-4Download citationReceived: 13 August 2024Accepted: 23 October 2024Published: 06 November 2024DOI: https://doi.org/10.1038/s41598-024-77575-4Share this articleAnyone you share the following link with will be able to read this content:Get shareable linkSorry, a shareable link is not currently available for this article.Copy to clipboard.

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Keywords2,2′:6′,2′′-terpyridineAnticancer activityReactive oxygen speciesOxidative stressApoptosisAutophagyCell cycle inhibition

关键词2,2'：6'，2''-三联吡啶抗癌活性反应性氧物种氧化应激细胞凋亡自噬细胞周期抑制

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BiochemistryCell biologyChemical biologyDrug discoveryMolecular biology

生物化学细胞生物化学生物药物发现分子生物学