Rafael Fonseca, Yasmin Dos Santos Louzano, Cindy Juliet Cristancho Ortiz, Matheus de Freitas Silva, Maria Luiza Vieira Felix, Guilherme Álvaro Ferreira-Silva, Ester Siqueira Caixeta, Bruno Zavan, Claudio Viegas, Marisa Ionta
{"title":"姜黄素样化合物通过诱导细胞周期阻滞和衰老抑制腺癌细胞增殖。","authors":"Rafael Fonseca, Yasmin Dos Santos Louzano, Cindy Juliet Cristancho Ortiz, Matheus de Freitas Silva, Maria Luiza Vieira Felix, Guilherme Álvaro Ferreira-Silva, Ester Siqueira Caixeta, Bruno Zavan, Claudio Viegas, Marisa Ionta","doi":"10.3390/ph18060914","DOIUrl":null,"url":null,"abstract":"<p><p><b>Background:</b> Lung cancer is the leading cause of cancer-related death in the male sex worldwide. Non-small cell lung cancer (NSCLC) is the most prevalent type, accounting for 80-85% of cases, and lung adenocarcinoma is the most common and lethal NSCLC subtype, being responsible for ca. 50% of deaths. Despite new therapeutic strategies, lung cancer mortality rates remain high, highlighting the need for the development of new drugs. <b>Objectives:</b> We investigated the pharmacological potential of a series of curcumin-like compounds using two lung adenocarcinoma cell lines as models. <b>Methods and Results:</b> Cell viability assay led to the identification of PQM-214 as the hit compound, and other methodologies were employed to investigate the mechanisms underlying its antitumor potential, including cell cycle analysis, mitotic index determination, assessment of clonogenic capacity, senescence-associated β-galactosidase and annexin V assays, quantitative PCR, and Western blot analyses. The mechanism of action of PQM-214 was investigated in A549 cells, revealing that it effectively inhibits cell proliferation by inducing cell cycle arrest, apoptosis, or senescence. Cell cycle key regulators were significantly modulated by PQM-214, with cyclin E2, <i>MYC</i>, and <i>FOXM1</i> being downregulated, while senescence markers such as cyclin D1, <i>CDKN1A</i> (p21), <i>IL-8</i>, <i>TIMP1</i>, and <i>TIMP2</i> were upregulated. Moreover, Western blot results revealed upregulation of cyclin D1 and p21 in PQM-214-treated samples, with a downregulation of cyclin B. <b>Conclusions</b>: PQM-214 seems to act on different molecular targets in lung adenocarcinoma cells, inhibiting cell proliferation and inducing apoptosis. Further studies will be conducted to explore whether PQM-214 can also act as a senolytic agent, which would reinforce its anticancer potential.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"18 6","pages":""},"PeriodicalIF":4.3000,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12196036/pdf/","citationCount":"0","resultStr":"{\"title\":\"Curcumin-like Compound Inhibits Proliferation of Adenocarcinoma Cells by Inducing Cell Cycle Arrest and Senescence.\",\"authors\":\"Rafael Fonseca, Yasmin Dos Santos Louzano, Cindy Juliet Cristancho Ortiz, Matheus de Freitas Silva, Maria Luiza Vieira Felix, Guilherme Álvaro Ferreira-Silva, Ester Siqueira Caixeta, Bruno Zavan, Claudio Viegas, Marisa Ionta\",\"doi\":\"10.3390/ph18060914\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p><b>Background:</b> Lung cancer is the leading cause of cancer-related death in the male sex worldwide. Non-small cell lung cancer (NSCLC) is the most prevalent type, accounting for 80-85% of cases, and lung adenocarcinoma is the most common and lethal NSCLC subtype, being responsible for ca. 50% of deaths. Despite new therapeutic strategies, lung cancer mortality rates remain high, highlighting the need for the development of new drugs. <b>Objectives:</b> We investigated the pharmacological potential of a series of curcumin-like compounds using two lung adenocarcinoma cell lines as models. <b>Methods and Results:</b> Cell viability assay led to the identification of PQM-214 as the hit compound, and other methodologies were employed to investigate the mechanisms underlying its antitumor potential, including cell cycle analysis, mitotic index determination, assessment of clonogenic capacity, senescence-associated β-galactosidase and annexin V assays, quantitative PCR, and Western blot analyses. The mechanism of action of PQM-214 was investigated in A549 cells, revealing that it effectively inhibits cell proliferation by inducing cell cycle arrest, apoptosis, or senescence. Cell cycle key regulators were significantly modulated by PQM-214, with cyclin E2, <i>MYC</i>, and <i>FOXM1</i> being downregulated, while senescence markers such as cyclin D1, <i>CDKN1A</i> (p21), <i>IL-8</i>, <i>TIMP1</i>, and <i>TIMP2</i> were upregulated. Moreover, Western blot results revealed upregulation of cyclin D1 and p21 in PQM-214-treated samples, with a downregulation of cyclin B. <b>Conclusions</b>: PQM-214 seems to act on different molecular targets in lung adenocarcinoma cells, inhibiting cell proliferation and inducing apoptosis. Further studies will be conducted to explore whether PQM-214 can also act as a senolytic agent, which would reinforce its anticancer potential.</p>\",\"PeriodicalId\":20198,\"journal\":{\"name\":\"Pharmaceuticals\",\"volume\":\"18 6\",\"pages\":\"\"},\"PeriodicalIF\":4.3000,\"publicationDate\":\"2025-06-18\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12196036/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Pharmaceuticals\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.3390/ph18060914\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"CHEMISTRY, MEDICINAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Pharmaceuticals","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.3390/ph18060914","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"CHEMISTRY, MEDICINAL","Score":null,"Total":0}
Curcumin-like Compound Inhibits Proliferation of Adenocarcinoma Cells by Inducing Cell Cycle Arrest and Senescence.
Background: Lung cancer is the leading cause of cancer-related death in the male sex worldwide. Non-small cell lung cancer (NSCLC) is the most prevalent type, accounting for 80-85% of cases, and lung adenocarcinoma is the most common and lethal NSCLC subtype, being responsible for ca. 50% of deaths. Despite new therapeutic strategies, lung cancer mortality rates remain high, highlighting the need for the development of new drugs. Objectives: We investigated the pharmacological potential of a series of curcumin-like compounds using two lung adenocarcinoma cell lines as models. Methods and Results: Cell viability assay led to the identification of PQM-214 as the hit compound, and other methodologies were employed to investigate the mechanisms underlying its antitumor potential, including cell cycle analysis, mitotic index determination, assessment of clonogenic capacity, senescence-associated β-galactosidase and annexin V assays, quantitative PCR, and Western blot analyses. The mechanism of action of PQM-214 was investigated in A549 cells, revealing that it effectively inhibits cell proliferation by inducing cell cycle arrest, apoptosis, or senescence. Cell cycle key regulators were significantly modulated by PQM-214, with cyclin E2, MYC, and FOXM1 being downregulated, while senescence markers such as cyclin D1, CDKN1A (p21), IL-8, TIMP1, and TIMP2 were upregulated. Moreover, Western blot results revealed upregulation of cyclin D1 and p21 in PQM-214-treated samples, with a downregulation of cyclin B. Conclusions: PQM-214 seems to act on different molecular targets in lung adenocarcinoma cells, inhibiting cell proliferation and inducing apoptosis. Further studies will be conducted to explore whether PQM-214 can also act as a senolytic agent, which would reinforce its anticancer potential.
PharmaceuticalsPharmacology, Toxicology and Pharmaceutics-Pharmaceutical Science
CiteScore
6.10
自引率
4.30%
发文量
1332
审稿时长
6 weeks
期刊介绍:
Pharmaceuticals (ISSN 1424-8247) is an international scientific journal of medicinal chemistry and related drug sciences.Our aim is to publish updated reviews as well as research articles with comprehensive theoretical and experimental details. Short communications are also accepted; therefore, there is no restriction on the maximum length of the papers.