Cytotoxic and Antiproliferative Effects of Fusaric Acid on Human Prostate Cancer Cell Lines PC-3 and LNCaP

Yıl 2025, Cilt: 35 Sayı: 6, 1266 - 1279, 31.12.2025

Neziha Senem Arı , Elif Önder , Mücahit Seçme

https://doi.org/10.54005/geneltip.1742631

Öz

Aim:
Fusaric acid (FA), a secondary metabolite derived from Fusarium species and structurally similar to picolinic acid, has recently attracted increasing interest due to its potential anticancer properties. This study aimed to investigate the cytotoxic, antiproliferative, apoptotic, and oxidative effects of FA on human prostate cancer cell lines PC-3 and LNCaP under in vitro conditions.
Methods:
PC-3 and LNCaP cells were exposed to increasing concentrations of FA and incubated for 48 hours. Cell viability was assessed using the XTT assay, and IC₅₀ values were calculated. Expression levels of apoptosis-related genes (CASP3, CASP8, CASP9, CASP10, BAX, BID, and BCL-2) were analyzed by quantitative real-time PCR (qRT-PCR). Proliferative and migratory behaviors were evaluated using colony formation and wound healing assays, respectively. Oxidative stress was assessed by measuring total oxidant status (TOS), total antioxidant status (TAS), and calculating the oxidative stress index (OSI).
Results:
The IC₅₀ values of FA were determined as 262.94 µM for PC-3 cells and 278.72 µM for LNCaP cells. FA treatment significantly increased the expression of pro-apoptotic genes, while reducing the expression of the anti-apoptotic gene BCL-2. Colony-forming capacity was markedly reduced following FA exposure, with no significant enhancement in wound closure. TOS levels significantly decreased in LNCaP cells, while OSI values declined in both cell lines. No statistically significant changes were observed in TAS levels.
Conclusion:
This study demonstrates that fusaric acid exerts pronounced antiproliferative and pro-apoptotic effects on prostate cancer cells, potentially through the modulation of oxidative stress. These findings support the potential use of FA as a therapeutic candidate in prostate cancer treatment.

Anahtar Kelimeler

Prostatic Neoplasms , Fusaric Acid , Apoptosis , Oxidative Stress , Cell Line , Tumor

Etik Beyan

This research involved in vitro experiments using commercially obtained human prostate cancer cell lines (PC-3 and LNCaP). As no human participants or live animals were involved, ethics committee approval was not required in accordance with institutional and international guidelines regarding cell culture-based studies.

Destekleyen Kurum

This research received no financial support from any academic, institutional, or commercial source.

Teşekkür

The authors have no acknowledgments to report for this study.

Fusarik Asidin İnsan Prostat Kanseri Hücre Hatları PC-3 ve LNCaP Üzerindeki Sitotoksik ve Antiproliferatif Etkileri

Öz

Amaç:
Pikolinik asit ile yapısal benzerlik gösteren ve Fusarium türlerinden türetilen sekonder bir metabolit olan fusarik asit (FA), son yıllarda antikanser etkileri nedeniyle dikkat çeken bileşikler arasında yer almaktadır. Bu çalışmada, FA’nın insan prostat kanseri hücre hatları olan PC-3 ve LNCaP üzerindeki sitotoksik, antiproliferatif, apoptotik ve oksidatif etkilerinin in vitro koşullarda değerlendirilmesi amaçlanmıştır.
Gereç ve Yöntemler:
PC-3 ve LNCaP hücreleri, farklı dozlarda FA ile 48 saat süreyle inkübe edilmiştir. Hücre canlılığı, XTT testi ile değerlendirilerek IC₅₀ değerleri hesaplanmıştır. Apoptoz ile ilişkili genlerin (CASP3, CASP8, CASP9, CASP10, BAX, BID, BCL-2) ekspresyon düzeyleri kantitatif RT-PCR (qRT-PCR) yöntemiyle analiz edilmiştir. Hücrelerin proliferatif kapasitesi koloni oluşum analiziyle, migrasyon yetenekleri ise yara iyileşme (scratch) testiyle belirlenmiştir. Oksidatif stres durumu, total oksidan seviye (TOS), total antioksidan seviye (TAS) ve oksidatif stres indeksi (OSI) hesaplanarak değerlendirilmiştir.
Bulgular:
FA’nın IC₅₀ değeri PC-3 hücreleri için 262,94 µM, LNCaP hücreleri için ise 278,72 µM olarak bulunmuştur. FA uygulaması, pro-apoptotik gen ekspresyonlarını anlamlı düzeyde artırırken, anti-apoptotik BCL-2 geninde düşüşe neden olmuştur. Koloni oluşumu belirgin şekilde azalırken, yara kapanmasında anlamlı bir iyileşme gözlenmemiştir. TOS düzeyleri LNCaP hücrelerinde anlamlı şekilde azalmış, OSI değerleri her iki hücre hattında da düşmüştür. TAS düzeylerinde ise istatistiksel olarak anlamlı bir değişiklik saptanmamıştır.
Sonuç:
Bu çalışma, fusarik asidin prostat kanseri hücrelerinde belirgin antiproliferatif, pro-apoptotik ve oksidatif stres düzenleyici etkiler gösterdiğini ortaya koymakta olup, FA’nın prostat kanseri tedavisinde potansiyel bir aday olabileceğini desteklemektedir.

Anahtar Kelimeler

Prostat Neoplazileri , Fusarik Asit , Apoptozis , Oksidatif Stres , Tümör Hücre Hattı

Etik Beyan

Bu çalışma, ticari olarak temin edilen insan prostat kanseri hücre hatları (PC-3 ve LNCaP) kullanılarak in vitro koşullarda gerçekleştirilmiştir. Çalışmada insan katılımcı veya canlı hayvan kullanılmadığı için, hücre kültürü temelli araştırmalar kapsamında etik kurul onayı gerekmemektedir.

Destekleyen Kurum

Bu araştırma, herhangi bir akademik, kurumsal veya ticari kaynaktan finansal destek almamıştır.

Teşekkür

Yazarlar bu çalışma ile ilgili herhangi bir teşekkür bildiriminde bulunmamaktadır.

Kaynakça

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