Antitumor Activity, Mechanisms of Action and Phytochemical Profiling of Sub-Fractions Obtained from <i>Ulex gallii</i> Planch. (Fabaceae): A Medicinal Plant from Galicia (Spain)
The plant kingdom serves as a valuable resource for cancer drug development. This study explored the antitumor activity of different sub-fractions (hexane, dichloromethane and methanol) of <i>U. gallii</i> (gorse) methanol extract in glioblastoma (U-87MG and U-373MG) and neuroblastoma (S...
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2025-02-01
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| author | Lucía Bada Hussain Shakeel Butt Elías Quezada Aitor Picos Helle Wangensteen Kari Tvete Inngjerdingen José Gil-Longo Dolores Viña |
| author_facet | Lucía Bada Hussain Shakeel Butt Elías Quezada Aitor Picos Helle Wangensteen Kari Tvete Inngjerdingen José Gil-Longo Dolores Viña |
| author_sort | Lucía Bada |
| collection | DOAJ |
| description | The plant kingdom serves as a valuable resource for cancer drug development. This study explored the antitumor activity of different sub-fractions (hexane, dichloromethane and methanol) of <i>U. gallii</i> (gorse) methanol extract in glioblastoma (U-87MG and U-373MG) and neuroblastoma (SH-SY5Y) cell lines, along with their phytochemical profiles. Cytotoxicity was evaluated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and lactate dehydrogenase (LDH) assays, and cell cycle arrest and apoptosis were assessed through flow cytometry and by measuring reactive oxygen species (ROS) and protein expression levels. D7 and D8 dichloromethane sub-fractions significantly reduced cell viability, triggered early apoptosis in SH-SY5Y and U-87MG cells and specifically increased ROS levels in U-87MG cells. Western blot analyses showed that D7 increased p53, caspase-3, caspase-8 and γH2AX expression in SH-SY5Y and U-87MG cells, while D8 specifically elevated p53 in SH-SY5Y cells and caspase-3 in both cell lines. In U-373 cells, D7 and D8 markedly reduced cell viability, with D8 inducing necrosis. Morphological changes indicative of apoptosis were also observed in all cell lines. Bioinformatic analysis of UHPLC-MS and GC-MS data tentatively identified 20 metabolites in D7 and 15 in D8, primarily flavonoids. HPLC-DAD confirmed isoprunetin and genistein as the most abundant in D7 and D8, respectively, both isolated and identified by NMR spectroscopy. Most of the flavonoids identified have been reported as antitumor agents, suggesting that these compounds may be responsible for the observed pharmacological activity. |
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| issn | 1420-3049 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | MDPI AG |
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| series | Molecules |
| spelling | doaj-art-22d81b9d68b344fca94e451c1b741f942025-08-20T02:03:41ZengMDPI AGMolecules1420-30492025-02-0130497210.3390/molecules30040972Antitumor Activity, Mechanisms of Action and Phytochemical Profiling of Sub-Fractions Obtained from <i>Ulex gallii</i> Planch. (Fabaceae): A Medicinal Plant from Galicia (Spain)Lucía Bada0Hussain Shakeel Butt1Elías Quezada2Aitor Picos3Helle Wangensteen4Kari Tvete Inngjerdingen5José Gil-Longo6Dolores Viña7Group of Pharmacology of Chronic Diseases (CD Pharma), Molecular Medicine and Chronic Diseases Research Centre (CIMUS), Universidade de Santiago de Compostela, 15782 Santiago de Compostela, SpainSection for Pharmaceutical Chemistry, Department of Pharmacy, University of Oslo, 0316 Oslo, NorwayDepartment of Pharmacology, Pharmacy and Pharmaceutical Technology, Faculty of Pharmacy, Universidade de Santiago de Compostela, 15782 Santiago de Compostela, SpainGroup of Pharmacology of Chronic Diseases (CD Pharma), Molecular Medicine and Chronic Diseases Research Centre (CIMUS), Universidade de Santiago de Compostela, 15782 Santiago de Compostela, SpainSection for Pharmaceutical Chemistry, Department of Pharmacy, University of Oslo, 0316 Oslo, NorwaySection for Pharmaceutical Chemistry, Department of Pharmacy, University of Oslo, 0316 Oslo, NorwayDepartment of Pharmacology, Pharmacy and Pharmaceutical Technology, Faculty of Pharmacy, Universidade de Santiago de Compostela, 15782 Santiago de Compostela, SpainGroup of Pharmacology of Chronic Diseases (CD Pharma), Molecular Medicine and Chronic Diseases Research Centre (CIMUS), Universidade de Santiago de Compostela, 15782 Santiago de Compostela, SpainThe plant kingdom serves as a valuable resource for cancer drug development. This study explored the antitumor activity of different sub-fractions (hexane, dichloromethane and methanol) of <i>U. gallii</i> (gorse) methanol extract in glioblastoma (U-87MG and U-373MG) and neuroblastoma (SH-SY5Y) cell lines, along with their phytochemical profiles. Cytotoxicity was evaluated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and lactate dehydrogenase (LDH) assays, and cell cycle arrest and apoptosis were assessed through flow cytometry and by measuring reactive oxygen species (ROS) and protein expression levels. D7 and D8 dichloromethane sub-fractions significantly reduced cell viability, triggered early apoptosis in SH-SY5Y and U-87MG cells and specifically increased ROS levels in U-87MG cells. Western blot analyses showed that D7 increased p53, caspase-3, caspase-8 and γH2AX expression in SH-SY5Y and U-87MG cells, while D8 specifically elevated p53 in SH-SY5Y cells and caspase-3 in both cell lines. In U-373 cells, D7 and D8 markedly reduced cell viability, with D8 inducing necrosis. Morphological changes indicative of apoptosis were also observed in all cell lines. Bioinformatic analysis of UHPLC-MS and GC-MS data tentatively identified 20 metabolites in D7 and 15 in D8, primarily flavonoids. HPLC-DAD confirmed isoprunetin and genistein as the most abundant in D7 and D8, respectively, both isolated and identified by NMR spectroscopy. Most of the flavonoids identified have been reported as antitumor agents, suggesting that these compounds may be responsible for the observed pharmacological activity.https://www.mdpi.com/1420-3049/30/4/972<i>U. gallii</i>sub-fractionsneuroblastomaglioblastomacell cycleapoptosis |
| spellingShingle | Lucía Bada Hussain Shakeel Butt Elías Quezada Aitor Picos Helle Wangensteen Kari Tvete Inngjerdingen José Gil-Longo Dolores Viña Antitumor Activity, Mechanisms of Action and Phytochemical Profiling of Sub-Fractions Obtained from <i>Ulex gallii</i> Planch. (Fabaceae): A Medicinal Plant from Galicia (Spain) Molecules <i>U. gallii</i> sub-fractions neuroblastoma glioblastoma cell cycle apoptosis |
| title | Antitumor Activity, Mechanisms of Action and Phytochemical Profiling of Sub-Fractions Obtained from <i>Ulex gallii</i> Planch. (Fabaceae): A Medicinal Plant from Galicia (Spain) |
| title_full | Antitumor Activity, Mechanisms of Action and Phytochemical Profiling of Sub-Fractions Obtained from <i>Ulex gallii</i> Planch. (Fabaceae): A Medicinal Plant from Galicia (Spain) |
| title_fullStr | Antitumor Activity, Mechanisms of Action and Phytochemical Profiling of Sub-Fractions Obtained from <i>Ulex gallii</i> Planch. (Fabaceae): A Medicinal Plant from Galicia (Spain) |
| title_full_unstemmed | Antitumor Activity, Mechanisms of Action and Phytochemical Profiling of Sub-Fractions Obtained from <i>Ulex gallii</i> Planch. (Fabaceae): A Medicinal Plant from Galicia (Spain) |
| title_short | Antitumor Activity, Mechanisms of Action and Phytochemical Profiling of Sub-Fractions Obtained from <i>Ulex gallii</i> Planch. (Fabaceae): A Medicinal Plant from Galicia (Spain) |
| title_sort | antitumor activity mechanisms of action and phytochemical profiling of sub fractions obtained from i ulex gallii i planch fabaceae a medicinal plant from galicia spain |
| topic | <i>U. gallii</i> sub-fractions neuroblastoma glioblastoma cell cycle apoptosis |
| url | https://www.mdpi.com/1420-3049/30/4/972 |
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