Curcumin-like Compound Inhibits Proliferation of Adenocarcinoma Cells by Inducing Cell Cycle Arrest and Senescence
<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...
Saved in:
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2025-06-01
|
| Series: | Pharmaceuticals |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1424-8247/18/6/914 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849432263450689536 |
|---|---|
| author | 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 |
| author_facet | 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 |
| author_sort | Rafael Fonseca |
| collection | DOAJ |
| description | <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. |
| format | Article |
| id | doaj-art-49a09af1f85c498cb7671fdae4f4d7e7 |
| institution | Kabale University |
| issn | 1424-8247 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceuticals |
| spelling | doaj-art-49a09af1f85c498cb7671fdae4f4d7e72025-08-20T03:27:25ZengMDPI AGPharmaceuticals1424-82472025-06-0118691410.3390/ph18060914Curcumin-like Compound Inhibits Proliferation of Adenocarcinoma Cells by Inducing Cell Cycle Arrest and SenescenceRafael Fonseca0Yasmin dos Santos Louzano1Cindy Juliet Cristancho Ortiz2Matheus de Freitas Silva3Maria Luiza Vieira Felix4Guilherme Álvaro Ferreira-Silva5Ester Siqueira Caixeta6Bruno Zavan7Claudio Viegas8Marisa Ionta9Laboratório de Avaliação de Protótipos Antitumorais (LAPAN), Instituto de Ciências Biomédicas, Universidade Federal de Alfenas (UNIFAL-MG), Alfenas 37130-001, BrazilLaboratório de Avaliação de Protótipos Antitumorais (LAPAN), Instituto de Ciências Biomédicas, Universidade Federal de Alfenas (UNIFAL-MG), Alfenas 37130-001, BrazilLaboratory of Research in Medicinal Chemistry (PeQuiM), Institute of Chemistry, Federal University of Alfenas, Alfenas 37133-840, BrazilLaboratório de Avaliação de Protótipos Antitumorais (LAPAN), Instituto de Ciências Biomédicas, Universidade Federal de Alfenas (UNIFAL-MG), Alfenas 37130-001, BrazilLaboratório de Avaliação de Protótipos Antitumorais (LAPAN), Instituto de Ciências Biomédicas, Universidade Federal de Alfenas (UNIFAL-MG), Alfenas 37130-001, BrazilLaboratório de Avaliação de Protótipos Antitumorais (LAPAN), Instituto de Ciências Biomédicas, Universidade Federal de Alfenas (UNIFAL-MG), Alfenas 37130-001, BrazilLaboratório de Avaliação de Protótipos Antitumorais (LAPAN), Instituto de Ciências Biomédicas, Universidade Federal de Alfenas (UNIFAL-MG), Alfenas 37130-001, BrazilLaboratório de Avaliação de Protótipos Antitumorais (LAPAN), Instituto de Ciências Biomédicas, Universidade Federal de Alfenas (UNIFAL-MG), Alfenas 37130-001, BrazilLaboratory of Research in Medicinal Chemistry (PeQuiM), Institute of Chemistry, Federal University of Alfenas, Alfenas 37133-840, BrazilLaboratório de Avaliação de Protótipos Antitumorais (LAPAN), Instituto de Ciências Biomédicas, Universidade Federal de Alfenas (UNIFAL-MG), Alfenas 37130-001, Brazil<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.https://www.mdpi.com/1424-8247/18/6/914non-small cell lung cancercurcumin-like compoundscell cycle arrestsenescence |
| spellingShingle | 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 Curcumin-like Compound Inhibits Proliferation of Adenocarcinoma Cells by Inducing Cell Cycle Arrest and Senescence Pharmaceuticals non-small cell lung cancer curcumin-like compounds cell cycle arrest senescence |
| title | Curcumin-like Compound Inhibits Proliferation of Adenocarcinoma Cells by Inducing Cell Cycle Arrest and Senescence |
| title_full | Curcumin-like Compound Inhibits Proliferation of Adenocarcinoma Cells by Inducing Cell Cycle Arrest and Senescence |
| title_fullStr | Curcumin-like Compound Inhibits Proliferation of Adenocarcinoma Cells by Inducing Cell Cycle Arrest and Senescence |
| title_full_unstemmed | Curcumin-like Compound Inhibits Proliferation of Adenocarcinoma Cells by Inducing Cell Cycle Arrest and Senescence |
| title_short | Curcumin-like Compound Inhibits Proliferation of Adenocarcinoma Cells by Inducing Cell Cycle Arrest and Senescence |
| title_sort | curcumin like compound inhibits proliferation of adenocarcinoma cells by inducing cell cycle arrest and senescence |
| topic | non-small cell lung cancer curcumin-like compounds cell cycle arrest senescence |
| url | https://www.mdpi.com/1424-8247/18/6/914 |
| work_keys_str_mv | AT rafaelfonseca curcuminlikecompoundinhibitsproliferationofadenocarcinomacellsbyinducingcellcyclearrestandsenescence AT yasmindossantoslouzano curcuminlikecompoundinhibitsproliferationofadenocarcinomacellsbyinducingcellcyclearrestandsenescence AT cindyjulietcristanchoortiz curcuminlikecompoundinhibitsproliferationofadenocarcinomacellsbyinducingcellcyclearrestandsenescence AT matheusdefreitassilva curcuminlikecompoundinhibitsproliferationofadenocarcinomacellsbyinducingcellcyclearrestandsenescence AT marialuizavieirafelix curcuminlikecompoundinhibitsproliferationofadenocarcinomacellsbyinducingcellcyclearrestandsenescence AT guilhermealvaroferreirasilva curcuminlikecompoundinhibitsproliferationofadenocarcinomacellsbyinducingcellcyclearrestandsenescence AT estersiqueiracaixeta curcuminlikecompoundinhibitsproliferationofadenocarcinomacellsbyinducingcellcyclearrestandsenescence AT brunozavan curcuminlikecompoundinhibitsproliferationofadenocarcinomacellsbyinducingcellcyclearrestandsenescence AT claudioviegas curcuminlikecompoundinhibitsproliferationofadenocarcinomacellsbyinducingcellcyclearrestandsenescence AT marisaionta curcuminlikecompoundinhibitsproliferationofadenocarcinomacellsbyinducingcellcyclearrestandsenescence |