Tilia species (linden) exert anti-cancer effects on MIA PaCa-2 cells through the modulation of oxidative stress and inflammation

Abstract This study investigated the anti-cancer effects of the chemically characterized Tilia species (linden) on MIA PaCa-2 cells by analyzing various cancer-triggering mechanisms, including oxidative stress and inflammation status. Extracts from the flowers, bracts, and inflorescences of T. corda...

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Main Authors: Gamze Yüksel, Yağmur Özhan, Dilara Güreşçi, Etil Güzelmeriç, Nisa Beril Şen, İpek Bedir, Onur Senol, Gizem Emre, Dilek Telci, Vilma Petrikaitė, Hande Sipahi
Format: Article
Language:English
Published: Nature Portfolio 2025-01-01
Series:Scientific Reports
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Online Access:https://doi.org/10.1038/s41598-025-86457-2
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author Gamze Yüksel
Yağmur Özhan
Dilara Güreşçi
Etil Güzelmeriç
Nisa Beril Şen
İpek Bedir
Onur Senol
Gizem Emre
Dilek Telci
Vilma Petrikaitė
Hande Sipahi
author_facet Gamze Yüksel
Yağmur Özhan
Dilara Güreşçi
Etil Güzelmeriç
Nisa Beril Şen
İpek Bedir
Onur Senol
Gizem Emre
Dilek Telci
Vilma Petrikaitė
Hande Sipahi
author_sort Gamze Yüksel
collection DOAJ
description Abstract This study investigated the anti-cancer effects of the chemically characterized Tilia species (linden) on MIA PaCa-2 cells by analyzing various cancer-triggering mechanisms, including oxidative stress and inflammation status. Extracts from the flowers, bracts, and inflorescences of T. cordata, T. platyphyllos, T. rubra, and T. tomentosa were evaluated for antioxidant activity; subsequently, their ability to mitigate inflammation was assessed through in vitro nitrite assays in LPS-induced RAW264.7 cells. The anticancer potentials of the extracts against MIA PaCa-2 pancreatic cancer cells were investigated in 2D (cytotoxic effect) and 3D (effect on spheroid growth) models in vitro. All investigated Tilia species displayed remarkable antioxidant activity and significantly inhibited LPS-induced nitrite, IL-6, and PGE2 production. Extract from T. rubra bracts showed the highest cytotoxic activity against MIA PaCa-2 cells with an IC50 value of 0.16 mg/mL, as well as the most significant delay on spheroid growth, which was further confirmed through the arrest in cell cycle. In the Annexin V cell death assays of T. rubra, cells treated with the flower extract exhibited the highest rate of necrotic population with 66.53%. Overall, our results highlight a potential use for Tilia extracts, particularly T. rubra, in pancreatic cancer treatment by modulating cell death.
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publishDate 2025-01-01
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spelling doaj-art-da75d87af5b54707a9741bf1c49a50e92025-01-26T12:23:54ZengNature PortfolioScientific Reports2045-23222025-01-0115111710.1038/s41598-025-86457-2Tilia species (linden) exert anti-cancer effects on MIA PaCa-2 cells through the modulation of oxidative stress and inflammationGamze Yüksel0Yağmur Özhan1Dilara Güreşçi2Etil Güzelmeriç3Nisa Beril Şen4İpek Bedir5Onur Senol6Gizem Emre7Dilek Telci8Vilma Petrikaitė9Hande Sipahi10Faculty of Pharmacy, Department of Toxicology, Yeditepe UniversityFaculty of Pharmacy, Department of Toxicology, Yeditepe UniversityFaculty of Pharmacy, Department of Toxicology, Yeditepe UniversityFaculty of Pharmacy, Department of Pharmacognosy, Yeditepe UniversityFaculty of Pharmacy, Department of Pharmacognosy, Yeditepe UniversityDepartment of Genetics and Bioengineering, Yeditepe UniversityEast Anatolian High Technology Research and Application Center (DAYTAM), Atatürk UniversityFaculty of Pharmacy, Department of Pharmaceutical Botany, Marmara UniversityDepartment of Genetics and Bioengineering, Yeditepe UniversityLithuanian University of Health SciencesFaculty of Pharmacy, Department of Toxicology, Yeditepe UniversityAbstract This study investigated the anti-cancer effects of the chemically characterized Tilia species (linden) on MIA PaCa-2 cells by analyzing various cancer-triggering mechanisms, including oxidative stress and inflammation status. Extracts from the flowers, bracts, and inflorescences of T. cordata, T. platyphyllos, T. rubra, and T. tomentosa were evaluated for antioxidant activity; subsequently, their ability to mitigate inflammation was assessed through in vitro nitrite assays in LPS-induced RAW264.7 cells. The anticancer potentials of the extracts against MIA PaCa-2 pancreatic cancer cells were investigated in 2D (cytotoxic effect) and 3D (effect on spheroid growth) models in vitro. All investigated Tilia species displayed remarkable antioxidant activity and significantly inhibited LPS-induced nitrite, IL-6, and PGE2 production. Extract from T. rubra bracts showed the highest cytotoxic activity against MIA PaCa-2 cells with an IC50 value of 0.16 mg/mL, as well as the most significant delay on spheroid growth, which was further confirmed through the arrest in cell cycle. In the Annexin V cell death assays of T. rubra, cells treated with the flower extract exhibited the highest rate of necrotic population with 66.53%. Overall, our results highlight a potential use for Tilia extracts, particularly T. rubra, in pancreatic cancer treatment by modulating cell death.https://doi.org/10.1038/s41598-025-86457-2Tilia speciesPhenolic profileAntioxidant activityAnti-inflammatory activityAnticancer activity3D spheroid model
spellingShingle Gamze Yüksel
Yağmur Özhan
Dilara Güreşçi
Etil Güzelmeriç
Nisa Beril Şen
İpek Bedir
Onur Senol
Gizem Emre
Dilek Telci
Vilma Petrikaitė
Hande Sipahi
Tilia species (linden) exert anti-cancer effects on MIA PaCa-2 cells through the modulation of oxidative stress and inflammation
Scientific Reports
Tilia species
Phenolic profile
Antioxidant activity
Anti-inflammatory activity
Anticancer activity
3D spheroid model
title Tilia species (linden) exert anti-cancer effects on MIA PaCa-2 cells through the modulation of oxidative stress and inflammation
title_full Tilia species (linden) exert anti-cancer effects on MIA PaCa-2 cells through the modulation of oxidative stress and inflammation
title_fullStr Tilia species (linden) exert anti-cancer effects on MIA PaCa-2 cells through the modulation of oxidative stress and inflammation
title_full_unstemmed Tilia species (linden) exert anti-cancer effects on MIA PaCa-2 cells through the modulation of oxidative stress and inflammation
title_short Tilia species (linden) exert anti-cancer effects on MIA PaCa-2 cells through the modulation of oxidative stress and inflammation
title_sort tilia species linden exert anti cancer effects on mia paca 2 cells through the modulation of oxidative stress and inflammation
topic Tilia species
Phenolic profile
Antioxidant activity
Anti-inflammatory activity
Anticancer activity
3D spheroid model
url https://doi.org/10.1038/s41598-025-86457-2
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