{"title":"揭示二维铜/钠复合物的独特作用:氧化应激对红细胞和细胞毒性、凋亡、耐药性和肺癌细胞炎症的影响。","authors":"Chenchen Li, Mostafa Heidari Majd, Ameneh Heidari, Zohreh Razmara, Dongdong Guo","doi":"10.2174/0118715206380073250811113008","DOIUrl":null,"url":null,"abstract":"<p><strong>Introduction: </strong>Copper complexes, as endogenous metals, have potential in cancer therapy, addressing issues associated with cisplatin. Since cisplatin uses Copper Transporter 1 (CTR1) for cellular entry, copper complexes may utilize this pathway to enhance transport efficiency.</p><p><strong>Methods: </strong>The Cu/Na dipicolinic acid complex was synthesized to assess its cytotoxicity, induction of apoptosis, drug resistance, and inflammation in cancerous and normal lung cells. The effects of oxidative stress on erythrocytes were also examined.</p><p><strong>Results: </strong>Cytotoxicity tests (MTT and SRB) showed superior inhibitory effects on A549 lung cancer cells compared to cisplatin, with no toxicity observed in MRC-5 normal lung fibroblast cells. Real-time PCR revealed increased caspase-3 expression (extrinsic apoptosis) for the complex compared to cisplatin, possibly due to CTR1- mediated entry. The complex did not induce drug resistance, as shown by AKT1 expression, and reduced TNF-α expression, preventing inflammation in normal cells. In contrast to cisplatin, the complex caused minimal oxidative stress in erythrocytes.</p><p><strong>Discussion: </strong>It can be concluded that the Cu/Na dipicolinic acid complex may be easily transported by CTR1 to malignant tumors, particularly lung cancer. This complex has the ability to inhibit cancer cell growth and induce apoptosis in lung cancer cells. Therefore, copper complexes show promise as potential therapeutic options for treating this type of cancer.</p><p><strong>Conclusion: </strong>The copper/sodium complex demonstrates enhanced therapeutic efficacy in lung cancer cells, requiring lower doses than cisplatin, while being safer for normal cells and erythrocytes.</p>","PeriodicalId":7934,"journal":{"name":"Anti-cancer agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.0000,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Unveiling the Distinct Effects of a Two-Dimensional Copper/Sodium Complex: Oxidative Stress on Erythrocytes and Cytotoxicity, Apoptosis, Drug Resistance, and Inflammation in Lung Cancer Cells.\",\"authors\":\"Chenchen Li, Mostafa Heidari Majd, Ameneh Heidari, Zohreh Razmara, Dongdong Guo\",\"doi\":\"10.2174/0118715206380073250811113008\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Introduction: </strong>Copper complexes, as endogenous metals, have potential in cancer therapy, addressing issues associated with cisplatin. Since cisplatin uses Copper Transporter 1 (CTR1) for cellular entry, copper complexes may utilize this pathway to enhance transport efficiency.</p><p><strong>Methods: </strong>The Cu/Na dipicolinic acid complex was synthesized to assess its cytotoxicity, induction of apoptosis, drug resistance, and inflammation in cancerous and normal lung cells. The effects of oxidative stress on erythrocytes were also examined.</p><p><strong>Results: </strong>Cytotoxicity tests (MTT and SRB) showed superior inhibitory effects on A549 lung cancer cells compared to cisplatin, with no toxicity observed in MRC-5 normal lung fibroblast cells. Real-time PCR revealed increased caspase-3 expression (extrinsic apoptosis) for the complex compared to cisplatin, possibly due to CTR1- mediated entry. The complex did not induce drug resistance, as shown by AKT1 expression, and reduced TNF-α expression, preventing inflammation in normal cells. In contrast to cisplatin, the complex caused minimal oxidative stress in erythrocytes.</p><p><strong>Discussion: </strong>It can be concluded that the Cu/Na dipicolinic acid complex may be easily transported by CTR1 to malignant tumors, particularly lung cancer. This complex has the ability to inhibit cancer cell growth and induce apoptosis in lung cancer cells. Therefore, copper complexes show promise as potential therapeutic options for treating this type of cancer.</p><p><strong>Conclusion: </strong>The copper/sodium complex demonstrates enhanced therapeutic efficacy in lung cancer cells, requiring lower doses than cisplatin, while being safer for normal cells and erythrocytes.</p>\",\"PeriodicalId\":7934,\"journal\":{\"name\":\"Anti-cancer agents in medicinal chemistry\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":3.0000,\"publicationDate\":\"2025-09-03\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Anti-cancer agents in medicinal chemistry\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.2174/0118715206380073250811113008\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"CHEMISTRY, MEDICINAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Anti-cancer agents in medicinal chemistry","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.2174/0118715206380073250811113008","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"CHEMISTRY, MEDICINAL","Score":null,"Total":0}
Unveiling the Distinct Effects of a Two-Dimensional Copper/Sodium Complex: Oxidative Stress on Erythrocytes and Cytotoxicity, Apoptosis, Drug Resistance, and Inflammation in Lung Cancer Cells.
Introduction: Copper complexes, as endogenous metals, have potential in cancer therapy, addressing issues associated with cisplatin. Since cisplatin uses Copper Transporter 1 (CTR1) for cellular entry, copper complexes may utilize this pathway to enhance transport efficiency.
Methods: The Cu/Na dipicolinic acid complex was synthesized to assess its cytotoxicity, induction of apoptosis, drug resistance, and inflammation in cancerous and normal lung cells. The effects of oxidative stress on erythrocytes were also examined.
Results: Cytotoxicity tests (MTT and SRB) showed superior inhibitory effects on A549 lung cancer cells compared to cisplatin, with no toxicity observed in MRC-5 normal lung fibroblast cells. Real-time PCR revealed increased caspase-3 expression (extrinsic apoptosis) for the complex compared to cisplatin, possibly due to CTR1- mediated entry. The complex did not induce drug resistance, as shown by AKT1 expression, and reduced TNF-α expression, preventing inflammation in normal cells. In contrast to cisplatin, the complex caused minimal oxidative stress in erythrocytes.
Discussion: It can be concluded that the Cu/Na dipicolinic acid complex may be easily transported by CTR1 to malignant tumors, particularly lung cancer. This complex has the ability to inhibit cancer cell growth and induce apoptosis in lung cancer cells. Therefore, copper complexes show promise as potential therapeutic options for treating this type of cancer.
Conclusion: The copper/sodium complex demonstrates enhanced therapeutic efficacy in lung cancer cells, requiring lower doses than cisplatin, while being safer for normal cells and erythrocytes.
期刊介绍:
Formerly: Current Medicinal Chemistry - Anti-Cancer Agents.
Anti-Cancer Agents in Medicinal Chemistry aims to cover all the latest and outstanding developments in medicinal chemistry and rational drug design for the discovery of anti-cancer agents.
Each issue contains a series of timely in-depth reviews and guest edited issues written by leaders in the field covering a range of current topics in cancer medicinal chemistry. The journal only considers high quality research papers for publication.
Anti-Cancer Agents in Medicinal Chemistry is an essential journal for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important developments in cancer drug discovery.