Flavonoids from Cirsium italicum (Savi) DC. reduce reactive oxygen species and modulate histone deacetylase activity in triple-negative breast cancer cells

Year 2025, Volume: 50 Issue: 3, 752 - 760

Bahadır Batar , Mehmet Kazancı , Ahmet Ensar Karaoğlu , Alperen Genç , Furkan Doğan , Zeynel Utku Reyhan , Dilara Ceren Çaba , Yasemin Günaydın , Muhammed Baran , Eslem Mortaş , Ayşe Nur Çakır , Ferhat Eyüp Yeşilmen , Ada Aslan , Öykü Canbulat , Büşra Berdibek , Elif Serdal , Merve Argon , Hilmican Çalışkan , Temine Şabudak , Birol Topçu

https://doi.org/10.17826/cumj.1669161

Abstract

Purpose: The present study aims to investigate the potential anti-cancer activities of flavonoid compounds from Cirsium italicum (Savi) DC. plants in breast cancer cells.
Materials and Methods: MDA-MB-231 triple-negative breast cancer (TNBC) cells were used to demonstrate reactive oxygen species (ROS) production effects and histone deacetylase (HDAC) inhibitory activity of flavonoids [5,3',4'-trihydroxy-7-methoxy isoflavone (Santal) (1), 5,5'',7''-trihydroxy-3,7-dimethoxy-4',4'''-O-biflavone (2), 6-2ʹ-dihydroxy-5-methoxy isoflavonone-4ʹ-O-α-D-glucopyranoside (3), (8,3',4',5'-tetrahydroxy-7-O-α-glycosyl isoflavone)-6-8''-(4'''-hydroxy-7''-O-α-glycosyl isoflavone) biflavone (4)] isolated from C. italicum.
Results: Significant differences in intracellular ROS levels were observed in MDA-MB-231 breast cancer cells treated with the compounds at concentrations of 0.06, 0.08, and 0.1 mg/ml. Compound 2 at 0.06 mg/ml, and compounds 2 and 4 at 0.08 and 0.1 mg/ml, induced a significant decrease in intracellular ROS levels compared to control cells. At a concentration of 0.06 mg/ml, compound 2 showed a mean value of 0.003±0.004. At 0.08 mg/ml, the mean values were 0.006±0.018 for compound 2 and 0.013±0.013 for compound 4. At 0.1 mg/ml, compound 2 and compound 4 exhibited mean values of 0.014±0.017 and 0.014±0.007, respectively. Even though all flavonoids inhibited HDAC activity, this inhibition was not statistically significant.
Conclusion: Among the flavonoids isolated from C. italicum, compounds 2 and 4 showed potential anticancer effects in breast cancer cells, potentially through modulation of intracellular ROS levels.

Keywords

Asteraceae , breast cancer , Cirsium italicum , flavonoid , histone deacetylase , reactive oxygen species

Cirsium italicum (Savi) DC.'den elde edilen flavonoidler üçlü negatif meme kanseri hücrelerinde reaktif oksijen türlerini azaltır ve histon deasetilaz aktivitesini modüle eder

Abstract

Amaç: Bu çalışma, Cirsium italicum (Savi) DC. bitkisinden elde edilen flavonoid bileşiklerin meme kanseri hücrelerindeki potansiyel anti-kanser aktivitelerini araştırmayı amaçlamaktadır.
Gereç ve Yöntem: MDA-MB-231 üçlü negatif meme kanseri hücreleri, Cirsium italicum'dan izole edilen flavonoidler [5,3',4'-trihidroksi-7-metoksi izoflavon (Santal) (1), 5,5'',7''-trihidroksi-3,7-dimetoksi-4',4'''-O-biflavon (2), 6-2ʹ-dihidroksi-5-metoksi izoflavonon-4ʹ-O-α-D-glukopiranozid (3), (8,3',4',5'-tetrahidroksi-7-O-α-glikozil izoflavon)-6-8''-(4'''-hidroksi-7''-O-α-glikozil izoflavon) biflavon (4)]; reaktif oksijen türleri (ROS) üretim etkilerini ve histon deasetilaz (HDAC) inhibitör aktivitesini göstermek için kullanıldı.
Bulgular: 0.06, 0.08 ve 0.1 konsantrasyonlarında uygulanan bileşiklerle muamele edilen MDA-MB-231 meme kanseri hücrelerinde, hücre içi ROS düzeylerinde anlamlı farklılıklar gözlemlendi. 0.06 mg/ml konsantrasyonunda uygulanan bileşik 2 ile, 0.08 ve 0.1 mg/ml konsantrasyonlarında uygulanan bileşik 2 ve 4’ün, kontrol hücrelerine kıyasla hücre içi ROS düzeylerinde anlamlı bir azalmaya yol açtığı gözlemlendi. 0.06 mg/ml konsantrasyonunda, bileşik 2’nin ortalama değeri 0.003±0.004 olarak ölçüldü. 0.08 mg/ml konsantrasyonunda, ortalama değerler bileşik 2 için 0.006±0.018 ve bileşik 4 için 0.013±0.013 olarak belirlendi. 0.1 mg/ml konsantrasyonunda ise, bileşik 2 ve bileşik 4 sırasıyla 0.014±0.017 ve 0.014±0.007 değerlerini gösterdi. Her ne kadar tüm flavonoidler HDAC aktivitesini inhibe etmiş olsa da, bu inhibisyon istatistiksel olarak anlamlı bulunmadı.
Sonuç: C. italicum bitkisinden izole edilen flavonoidler arasında, bileşik 2 ve 4 hücre içi ROS düzeylerini modüle etme yoluyla meme kanseri hücrelerinde potansiyel antikanser etkiler gösterdi.

Keywords

Asteraceae , meme kanseri , Cirsium italicum , flavonoid , histon deasetilaz , reaktif oksijen türleri

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