Berberine enhances the therapeutic effect of 5-fluorouracil in Caco-2 colorectal adenocarcinoma cells by alleviating inflammation and inducing apoptosis

Seyma Oncu; Merve Becit-kizilkaya; Serkan Şen; Fatma Özlem Kargın Solmaz; Sefa Çelik

doi:10.17826/cumj.1344952

EN TR

Berberine enhances the therapeutic effect of 5-fluorouracil in Caco-2 colorectal adenocarcinoma cells by alleviating inflammation and inducing apoptosis

Abstract

Purpose: This study aims to investigate whether berberine (BBR) and 5-fluorouracil (5FU), which forms the backbone of chemotherapy, have a synergistic effect on colorectal adenocarcinoma cells (Caco-2) and what mechanisms might be behind this. Materials and Methods: Cell viability was determined by MTT and the combination index (CI) by Chou-Talalay method. Apoptosis and inflammation-related proteins (Bcl-2, p53, IL-6, TNF-α, MMP-9) were measured by ELISA. Results: The IC50 values of BBR and 5FU were found to be 280 µM and 20 mM for 24 h. The combination treatment showed synergistic cytotoxicity, both of which were more pronounced at IC50 (CI=0.143). 5FU+BBR showed a synergistic apoptotic effect by decreasing Bcl-2 and increasing p53 (0.712-fold decrease in Bcl-2 and 2.650-fold increase in p53 compared to 5FU). The increase in IL-6 and TNF-α by 5FU was significantly suppressed by 5FU+BBR (0.733-fold and 0.485-fold). Although there was no significant difference in MMP-9 in 5FU compared to control, 5FU+BBR significantly decreased MMP-9 (0.601-fold). Conclusion: The results show the enormous potential of BBR in combination with 5FU for the chemotherapy of colorectal carcinoma through apoptosis induction, inflammation inhibition and metastasis inhibition.

Keywords

berberine (BBR) , 5-fluorouracil (5FU) , synergism , Caco-2 , apoptosis , MMP-9

Berberin inflamasyon baskılanması ve apoptoz indüksiyonu ile Caco-2 kolorektal adenokarsinom hücrelerinde 5-florourasil'in terapötik etkisini arttırır

Öz

Amaç: Bu çalışma, berberin (BBR) ile kemoterapinin omurgasını oluşturan 5-fluorourasil (5FU)’in Caco-2 kolorektal adenokarsinoma hücreleri üzerinde sinerjik etki gösterip göstermediğini ve olası mekanizmalarını araştırmayı amaçlamaktadır. Gereç ve Yöntem: Hücre canlılığı MTT yöntemiyle ve kombinasyon indeksi (CI) Chou-Talalay yöntemiyle belirlendi. Apoptoz ve inflamasyonla ilişkili proteinlerin (Bcl-2, p53, IL-6, TNF-α, MMP-9) konsantrasyonları ELISA ile ölçüldü. Bulgular: BBR ve 5FU’nun IC50 değerleri 24 saat için 280 µM ve 20 mM olarak bulundu. Kombinasyon tedavi, her ikisinin de IC50 konsantrasyonlarında daha belirgin olmak üzere, sinerjik sitotoksik etki gösterdi (CI= 0.143). 5FU+BBR, Bcl-2’yi azaltarak ve p53’ü artırarak sinerjistik apoptotik etki gösterdi (5FU ile karşılaştırıldığında, Bcl-2 için 0.712 kat azalış ve p53 için 2.650 kat artış). Ayrıca, 5FU ile artan IL-6 ve TNF-α düzeyleri, 5FU+BBR tedavisi ile belirgin şekilde baskılandı (0.733 kat ve 0.485 kat). Ek olarak, 5FU ile tedavi edilen hücrelerde kontrol grubuna göre MMP-9 düzeylerinde anlamlı bir fark yokken, kombine tedavi MMP-9 düzeylerini belirgin şekilde (0.601 kat) azalttı. Sonuç: Bulgular, BBR’nin 5FU ile birlikte kolorektal kanseri kemoterapisi için apoptoz indüksiyonu, inflamasyon baskılaması ve metastaz inhibisyonuyla muazzam potansiyelini ortaya koymaktadır.

Anahtar Kelimeler

Berberin (BBR) , 5-fluorourasil (5FU) , sinerjizm , Caco-2 , apoptosis , MMP-9

Kaynakça

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Ayrıntılar

Birincil Dil

İngilizce

Konular

Kanser Hücre Biyolojisi , Kemoterapi , Moleküler Hedefler

Bölüm

Araştırma Makalesi

Yazarlar

Seyma Oncu
0000-0003-2468-2416
Türkiye

Merve Becit-kizilkaya ^*
0000-0002-8084-4419
Türkiye

Serkan Şen
0000-0002-2884-4753
Türkiye

Fatma Özlem Kargın Solmaz
0000-0002-3908-3371
Türkiye

Sefa Çelik
0000-0002-5187-378X
Türkiye

Yayımlanma Tarihi

29 Aralık 2023

Gönderilme Tarihi

17 Ağustos 2023

Kabul Tarihi

13 Kasım 2023

Yayımlandığı Sayı

Yıl 2023 Cilt: 48 Sayı: 4

DOI

https://doi.org/10.17826/cumj.1344952

IZ

https://izlik.org/JA52TM74GT

MLA

Oncu, Seyma, vd. “Berberine enhances the therapeutic effect of 5-fluorouracil in Caco-2 colorectal adenocarcinoma cells by alleviating inflammation and inducing apoptosis”. Cukurova Medical Journal, c. 48, sy 4, Aralık 2023, ss. 1238-47, doi:10.17826/cumj.1344952.