Selective cytotoxicity of ferulic acid-loaded ZIF-8 nanoparticles and free Ferulic Acid on ovarian carcinoma and dental pulp stem cells

Elif Önder; Nazlı Çil; Hasan İlhan; Hande Şenol; Gülçin Abban Mete

doi:10.31362/patd.1977665

TR EN

Ferulik asit içeren ZIF-8 nanopartiküllerinin ve serbest ferulik asidin ovaryum karsinomu ve diş pulpa kök hücreleri üzerindeki seçici sitotoksisitesi

Öz

Amaç: Düşük stabilitesi nedeniyle klinik kullanımı sınırlı olan ferulik asidin (FA) hücre içi taşınımını iyileştirmek amacıyla pH'a duyarlı zeolitik imidazolat çerçeve-8 (ZIF-8) gibi nano-metal-organik çerçeveler kullanılmış ve FA-ZIF-8 nanopartikülleri tasarlanarak bu sistemin over kanseri hatlarında seçici sitotoksik, anti-migratif ve apoptotik etkileri sağlıklı dental pulpa kök hücreleri (DPSCs) kontrolü eşliğinde in vitro olarak değerlendirilmiştir.
Yöntemler: FA-ZIF-8 nanopartikülleri sentezlenmiş ve karakterize edilmiştir. OVCAR-3, SKOV-3 ve DPSCs, 72 saate kadar serbest FA (5 μM–1 mM) ve FA-ZIF-8'in (25–500 μg/mL) artan konsantrasyonlarına maruz bırakılmıştır. IC50 değerleri XTT analizi ile belirlenmiştir. Apoptotik belirteçler sırasıyla qRT-PCR, immünositokimya ve TUNEL analizi ile doğrulanmıştır. Uzun vadeli üreme yeteneği ve lateral hücre hareketliliği sırasıyla koloni ve yara iyileşmesi analizleri ile izlenmiştir.
Bulgular: Tek başına uygulanan serbest FA, toksik olmayan bir profil sergilemiş; hem kanser hatlarının hem de DPSC'lerin proliferasyonunu aktif olarak uyarmıştır. FA-ZIF-8 bu yanıtı tersine çevirerek, OVCAR-3 için 48 saatlik IC50 değerini 308,2098 μg/mL ve SKOV-3 için 336,3022 μg/mL olarak belirledi. FA-ZIF-8, Bcl-2'yi baskılarken Bax ekspresyonunu ve Caspase-3 düzeylerini artırdı ve bu da Bax/Bcl-2 oranında anlamlı bir artışa yol açtı (p=0,0024). Bu sonuçlar, TUNEL pozitif apoptotik hücre sayılarındaki istatistiksel olarak anlamlı artışla onaylanmıştır. Ayrıca FA-ZIF-8, koloni oluşumunu kısıtlamış ve özellikle SKOV-3 hatlarında lateral göç indekslerini anlamlı olarak azaltılmıştır.

Sonuç: FA proliferatif bir ligand gibi davranırken, FA-ZIF-8 nanopartikülleri şeklindeki stratejik formülasyonunun bir "Truva Atı" etkisi yarattığını; epitelyal over kanseri hücrelerine seçici sitotoksisite, anti-metastatik baskılama ve pH'a duyarlı apoptotik, indüksiyon sağladığı görülmüştür.

Anahtar Kelimeler

Zeolitik imidazolat çerçeve-8, over kanseri, ferulik asit, apoptosis, yara iyileşmesi

Etik Beyan

Bu çalışma,Pamukkale Üniversitesi Non-İnvaziv Klinik Araştırmalar Etik Kurulu tarafından onaylanmıştır (onay tarihi: 13.03.2026, onay numarası: E-60116787-020-845567).

Selective cytotoxicity of ferulic acid-loaded ZIF-8 nanoparticles and free Ferulic Acid on ovarian carcinoma and dental pulp stem cells

Öz

Purpose: To overcome the rapid oxidation and low stability of Ferulic Acid (FA), this study designed and characterized FA-loaded Zeolitic imidazol framework -8 (FA-ZIF-8) nanoparticles, evaluating their selective cytotoxic, anti-proliferative, anti-migratory, and apoptotic effects on OVCAR-3 and SKOV-3 ovarian cancer cells alongside healthy primary dental pulp stem cells (DPSCs).
Materials and methods: FA-ZIF-8 nanoparticles were synthesized and characterized. OVCAR-3, SKOV-3, and DPSC cohorts were treated with varying concentrations of FA (5 μM–1 mM) and FA-ZIF-8 (25–500 μg/mL) for up to 72 h. Cell viability and 48-h half-maximal inhibitory concentrations IC50 were quantified using the XTT assay. Transcriptional and translational expressions of apoptotic markers were analyzed via qRT-PCR and immunocytochemistry and TUNEL analysis. Long-term survival and lateral cell motility were monitored via coloni and scratch wound healing assays.
Results: FA exhibited a non-toxic profile, actively stimulating the proliferation of both cancer lines and DPSCs. FA-ZIF-8 inverted this response, yielding 48-h IC50 values of 308.2098 μg/mL for OVCAR-3 and 336.3022 μg/mL for SKOV-3. FA-ZIF-8 upregulated Bax expression and Caspase-3 levels while suppressing Bcl-2, driving a significant increase in the Bax/Bcl-2 (p=0.0024). These results were confirmed by an increase in TUNEL-positive apoptotic cell. Furthermore, FA-ZIF-8 inhibited colony formation and significantly reduced lateral migration indices, particularly in SKOV-3 lines.
Conclusion: FA acts as a proliferative ligand, its strategic formulation into FA-ZIF-8 nanoparticles enables a, "Trojan Horse" effect, delivering selective cytotoxicity, anti-metastatic suppression, pH-responsive apoptotic induction to epithelial ovarian cancer cells.

Anahtar Kelimeler

Zeolitic imidazol framework 8, ovarian cancer, ferulic acid, apoptosis, wound healing

Etik Beyan

This study was approved by Pamukkale University Ethic Committee for Non-Invasive Clinical Trials (approved date: 13.03.2026, and approved number: E-60116787-020-845567).

Kaynakça

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Ayrıntılar

Birincil Dil

İngilizce

Konular

Biyokimya ve Hücre Biyolojisi (Diğer), Kadın Hastalıkları ve Doğum

Bölüm

Araştırma Makalesi

Yazarlar

Elif Önder
0000-0002-7187-1669
Türkiye

Nazlı Çil ^*
0000-0002-2164-8688
Türkiye

Hasan İlhan
0000-0002-4475-1629
Türkiye

Hande Şenol
0000-0001-6395-7924
Türkiye

Gülçin Abban Mete
0000-0001-6794-3685
Türkiye

Yayımlanma Tarihi

10 Ekim 2026

Gönderilme Tarihi

24 Haziran 2026

Kabul Tarihi

9 Ekim 2026

Yayımlandığı Sayı

Yıl 2026 Cilt: 19 Sayı: 4

DOI

https://doi.org/10.31362/patd.1977665

IZ

https://izlik.org/JA24PW49CT

APA

Önder, E., Çil, N., İlhan, H., Şenol, H., & Abban Mete, G. (2026). Selective cytotoxicity of ferulic acid-loaded ZIF-8 nanoparticles and free Ferulic Acid on ovarian carcinoma and dental pulp stem cells. Pamukkale Medical Journal, 19(4), 834-849. https://doi.org/10.31362/patd.1977665

AMA

1.Önder E, Çil N, İlhan H, Şenol H, Abban Mete G. Selective cytotoxicity of ferulic acid-loaded ZIF-8 nanoparticles and free Ferulic Acid on ovarian carcinoma and dental pulp stem cells. Pam Tıp Derg. 2026;19(4):834-849. doi:10.31362/patd.1977665

Chicago

Önder, Elif, Nazlı Çil, Hasan İlhan, Hande Şenol, ve Gülçin Abban Mete. 2026. “Selective cytotoxicity of ferulic acid-loaded ZIF-8 nanoparticles and free Ferulic Acid on ovarian carcinoma and dental pulp stem cells”. Pamukkale Medical Journal 19 (4): 834-49. https://doi.org/10.31362/patd.1977665.

EndNote

Önder E, Çil N, İlhan H, Şenol H, Abban Mete G (01 Ekim 2026) Selective cytotoxicity of ferulic acid-loaded ZIF-8 nanoparticles and free Ferulic Acid on ovarian carcinoma and dental pulp stem cells. Pamukkale Medical Journal 19 4 834–849.

IEEE

[1]E. Önder, N. Çil, H. İlhan, H. Şenol, ve G. Abban Mete, “Selective cytotoxicity of ferulic acid-loaded ZIF-8 nanoparticles and free Ferulic Acid on ovarian carcinoma and dental pulp stem cells”, Pam Tıp Derg, c. 19, sy 4, ss. 834–849, Eki. 2026, doi: 10.31362/patd.1977665.

ISNAD

Önder, Elif - Çil, Nazlı - İlhan, Hasan - Şenol, Hande - Abban Mete, Gülçin. “Selective cytotoxicity of ferulic acid-loaded ZIF-8 nanoparticles and free Ferulic Acid on ovarian carcinoma and dental pulp stem cells”. Pamukkale Medical Journal 19/4 (01 Ekim 2026): 834-849. https://doi.org/10.31362/patd.1977665.

JAMA

1.Önder E, Çil N, İlhan H, Şenol H, Abban Mete G. Selective cytotoxicity of ferulic acid-loaded ZIF-8 nanoparticles and free Ferulic Acid on ovarian carcinoma and dental pulp stem cells. Pam Tıp Derg. 2026;19:834–849.

MLA

Önder, Elif, vd. “Selective cytotoxicity of ferulic acid-loaded ZIF-8 nanoparticles and free Ferulic Acid on ovarian carcinoma and dental pulp stem cells”. Pamukkale Medical Journal, c. 19, sy 4, Ekim 2026, ss. 834-49, doi:10.31362/patd.1977665.

Vancouver

1.Elif Önder, Nazlı Çil, Hasan İlhan, Hande Şenol, Gülçin Abban Mete. Selective cytotoxicity of ferulic acid-loaded ZIF-8 nanoparticles and free Ferulic Acid on ovarian carcinoma and dental pulp stem cells. Pam Tıp Derg. 01 Ekim 2026;19(4):834-49. doi:10.31362/patd.1977665

Pamukkale Medical Journal Creative Commons Atıf-GayriTicari 4.0 Uluslararası Lisansı (CC BY NC) ile lisanslanmıştır.

Ferulik asit içeren ZIF-8 nanopartiküllerinin ve serbest ferulik asidin ovaryum karsinomu ve diş pulpa kök hücreleri üzerindeki seçici sitotoksisitesi

Öz

Anahtar Kelimeler

Etik Beyan

Selective cytotoxicity of ferulic acid-loaded ZIF-8 nanoparticles and free Ferulic Acid on ovarian carcinoma and dental pulp stem cells

Öz

Anahtar Kelimeler

Etik Beyan

Kaynakça

Ayrıntılar

Birincil Dil

Konular

Bölüm

Yazarlar

Yayımlanma Tarihi

Gönderilme Tarihi

Kabul Tarihi

Yayımlandığı Sayı

DOI

IZ

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