Mohamed M. El-bendary, Abdullah Akhdhar, Abdullah S. Al-Bogami, Doaa Domyati, Abdulaziz A. Kalantan, Faisal Ay Alzahrani, Samer M. Alamoudi, Ryan A. Sheikh, Ehab M. M. Ali
{"title":"基于吡啶碱的钯和铂络合物通过癌细胞中的凋亡蛋白信号诱导抗癌效果。","authors":"Mohamed M. El-bendary, Abdullah Akhdhar, Abdullah S. Al-Bogami, Doaa Domyati, Abdulaziz A. Kalantan, Faisal Ay Alzahrani, Samer M. Alamoudi, Ryan A. Sheikh, Ehab M. M. Ali","doi":"10.1007/s10534-023-00580-z","DOIUrl":null,"url":null,"abstract":"<div><p>Palladium and platinum complexes, especially those that include cisplatin, can be useful chemotherapeutic drugs. Alternatives that have less adverse effects and require lower dosages of treatment could be provided by complexes containing pyridine bases. The complexes <b>[Pd(SCN)</b><sub><b>2</b></sub><b>(4-Acpy)</b><sub><b>2</b></sub><b>] (1), [Pd(N</b><sub><b>3</b></sub><b>)</b><sub><b>2</b></sub><b>(4-Acpy)</b><sub><b>2</b></sub><b>] (2) [Pd(paOH)</b><sub><b>2</b></sub><b>].2Cl</b> (<b>3</b>) <b>and [Pt(SCN)</b><sub><b>2</b></sub><b>(paO)</b><sub><b>2</b></sub><b>] (4)</b> were prepared by self-assembly method at ambient temperature; (4-Acpy = 4-acetylpyridine and paOH = pyridine-2-carbaldehyde-oxime). The structure of complexes <b>1–4</b> was confirmed using spectroscopic and X-ray crystallography methods. Complexes <b>1–4</b> have similar features in isomerism that include the <i>trans</i> coordination geometry of pyridine ligands with Pd or Pt ion. The 3D network structure of complexes <b>1–4</b> was constructed by an infinite number of discrete mononuclear molecules extending via H-bonds. The Pd and Pt complexes <b>1–4</b> with pyridine ligands were assessed on MCF-7, T47D breast cancer cells and HCT116 colon cancer cells. The study evaluated cell death through apoptosis and cell cycle phases in MCF-7 cells treated with palladium or platinum conjugated with pyridine base. Upon treatment of MCF-7 with these complexes, the expression of apoptotic signals (Bcl2, p53, Bax and c-Myc) and cell cycle signals (p16, CDK1A, CDK1B) were evaluated. Compared to other complexes and cisplatin, IC<sub>50</sub> of complex <b>1</b> was lowest in MCF-7 cells and complex <b>2</b> in T47D cells. Complex <b>4</b> has the highest effectiveness on HCT116. The selective index (SI) of complexes <b>1–4</b> has a value of more than two for all cancer cell lines, indicating that the complexes were less toxic to normal cells when given the same dose. MCF-7 cells treated with complex <b>2</b> and platinum complex <b>4</b> exhibited the highest level of early apoptosis. p16 may be signal arrest cells in Sub G, which was observed in cells treated with palladium complexes that suppress excessive cell proliferation. High c-Myc expression of treated cells with four complexes <b>1–4</b> and cisplatin could induce p53. All complexes <b>1–4</b> elevated the expression of Bax and triggered by the tumor suppressor gene p53. p53 was downregulating the expression of Bcl2.</p></div>","PeriodicalId":491,"journal":{"name":"Biometals","volume":null,"pages":null},"PeriodicalIF":4.1000,"publicationDate":"2024-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Palladium and platinum complexes based on pyridine bases induced anticancer effectiveness via apoptosis protein signaling in cancer cells\",\"authors\":\"Mohamed M. El-bendary, Abdullah Akhdhar, Abdullah S. Al-Bogami, Doaa Domyati, Abdulaziz A. Kalantan, Faisal Ay Alzahrani, Samer M. Alamoudi, Ryan A. Sheikh, Ehab M. M. Ali\",\"doi\":\"10.1007/s10534-023-00580-z\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p>Palladium and platinum complexes, especially those that include cisplatin, can be useful chemotherapeutic drugs. Alternatives that have less adverse effects and require lower dosages of treatment could be provided by complexes containing pyridine bases. The complexes <b>[Pd(SCN)</b><sub><b>2</b></sub><b>(4-Acpy)</b><sub><b>2</b></sub><b>] (1), [Pd(N</b><sub><b>3</b></sub><b>)</b><sub><b>2</b></sub><b>(4-Acpy)</b><sub><b>2</b></sub><b>] (2) [Pd(paOH)</b><sub><b>2</b></sub><b>].2Cl</b> (<b>3</b>) <b>and [Pt(SCN)</b><sub><b>2</b></sub><b>(paO)</b><sub><b>2</b></sub><b>] (4)</b> were prepared by self-assembly method at ambient temperature; (4-Acpy = 4-acetylpyridine and paOH = pyridine-2-carbaldehyde-oxime). The structure of complexes <b>1–4</b> was confirmed using spectroscopic and X-ray crystallography methods. Complexes <b>1–4</b> have similar features in isomerism that include the <i>trans</i> coordination geometry of pyridine ligands with Pd or Pt ion. The 3D network structure of complexes <b>1–4</b> was constructed by an infinite number of discrete mononuclear molecules extending via H-bonds. The Pd and Pt complexes <b>1–4</b> with pyridine ligands were assessed on MCF-7, T47D breast cancer cells and HCT116 colon cancer cells. The study evaluated cell death through apoptosis and cell cycle phases in MCF-7 cells treated with palladium or platinum conjugated with pyridine base. Upon treatment of MCF-7 with these complexes, the expression of apoptotic signals (Bcl2, p53, Bax and c-Myc) and cell cycle signals (p16, CDK1A, CDK1B) were evaluated. Compared to other complexes and cisplatin, IC<sub>50</sub> of complex <b>1</b> was lowest in MCF-7 cells and complex <b>2</b> in T47D cells. Complex <b>4</b> has the highest effectiveness on HCT116. The selective index (SI) of complexes <b>1–4</b> has a value of more than two for all cancer cell lines, indicating that the complexes were less toxic to normal cells when given the same dose. MCF-7 cells treated with complex <b>2</b> and platinum complex <b>4</b> exhibited the highest level of early apoptosis. p16 may be signal arrest cells in Sub G, which was observed in cells treated with palladium complexes that suppress excessive cell proliferation. High c-Myc expression of treated cells with four complexes <b>1–4</b> and cisplatin could induce p53. All complexes <b>1–4</b> elevated the expression of Bax and triggered by the tumor suppressor gene p53. p53 was downregulating the expression of Bcl2.</p></div>\",\"PeriodicalId\":491,\"journal\":{\"name\":\"Biometals\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":4.1000,\"publicationDate\":\"2024-02-15\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Biometals\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://link.springer.com/article/10.1007/s10534-023-00580-z\",\"RegionNum\":3,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"BIOCHEMISTRY & MOLECULAR BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Biometals","FirstCategoryId":"99","ListUrlMain":"https://link.springer.com/article/10.1007/s10534-023-00580-z","RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
Palladium and platinum complexes based on pyridine bases induced anticancer effectiveness via apoptosis protein signaling in cancer cells
Palladium and platinum complexes, especially those that include cisplatin, can be useful chemotherapeutic drugs. Alternatives that have less adverse effects and require lower dosages of treatment could be provided by complexes containing pyridine bases. The complexes [Pd(SCN)2(4-Acpy)2] (1), [Pd(N3)2(4-Acpy)2] (2) [Pd(paOH)2].2Cl (3) and [Pt(SCN)2(paO)2] (4) were prepared by self-assembly method at ambient temperature; (4-Acpy = 4-acetylpyridine and paOH = pyridine-2-carbaldehyde-oxime). The structure of complexes 1–4 was confirmed using spectroscopic and X-ray crystallography methods. Complexes 1–4 have similar features in isomerism that include the trans coordination geometry of pyridine ligands with Pd or Pt ion. The 3D network structure of complexes 1–4 was constructed by an infinite number of discrete mononuclear molecules extending via H-bonds. The Pd and Pt complexes 1–4 with pyridine ligands were assessed on MCF-7, T47D breast cancer cells and HCT116 colon cancer cells. The study evaluated cell death through apoptosis and cell cycle phases in MCF-7 cells treated with palladium or platinum conjugated with pyridine base. Upon treatment of MCF-7 with these complexes, the expression of apoptotic signals (Bcl2, p53, Bax and c-Myc) and cell cycle signals (p16, CDK1A, CDK1B) were evaluated. Compared to other complexes and cisplatin, IC50 of complex 1 was lowest in MCF-7 cells and complex 2 in T47D cells. Complex 4 has the highest effectiveness on HCT116. The selective index (SI) of complexes 1–4 has a value of more than two for all cancer cell lines, indicating that the complexes were less toxic to normal cells when given the same dose. MCF-7 cells treated with complex 2 and platinum complex 4 exhibited the highest level of early apoptosis. p16 may be signal arrest cells in Sub G, which was observed in cells treated with palladium complexes that suppress excessive cell proliferation. High c-Myc expression of treated cells with four complexes 1–4 and cisplatin could induce p53. All complexes 1–4 elevated the expression of Bax and triggered by the tumor suppressor gene p53. p53 was downregulating the expression of Bcl2.
期刊介绍:
BioMetals is the only established journal to feature the important role of metal ions in chemistry, biology, biochemistry, environmental science, and medicine. BioMetals is an international, multidisciplinary journal singularly devoted to the rapid publication of the fundamental advances of both basic and applied research in this field. BioMetals offers a forum for innovative research and clinical results on the structure and function of:
- metal ions
- metal chelates,
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- biominerals in all biosystems.
- BioMetals rapidly publishes original articles and reviews.
BioMetals is a journal for metals researchers who practice in medicine, biochemistry, pharmacology, toxicology, microbiology, cell biology, chemistry, and plant physiology who are based academic, industrial and government laboratories.