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

Article Details

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

Authors:

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

Publisher:

Cukurova University

Main Topics:

Kanser Hücre Biyolojisi | Kemoterapi | Moleküler Hedefler

Journal:

Cukurova Medical Journal Vol.48 Issue 4, pp.1238-1247

Document Type:

Article

Publication Date:

12/2023

Document Language:

English

Document ID (Org No.):

2001286421

pISSN:

2602-3032

Keywords:

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 CI0.143. 5FUBBR 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 5FUBBR 0.733-fold and 0.485-fold. Although there was no significant difference in MMP-9 in 5FU compared to control, 5FUBBR 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.

 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 CI0.143. 5FUBBR 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 5FUBBR 0.733-fold and 0.485-fold. Although there was no significant difference in MMP-9 in 5FU compared to control, 5FUBBR 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.

 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 CI0.143. 5FUBBR 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 5FUBBR 0.733-fold and 0.485-fold. Although there was no significant difference in MMP-9 in 5FU compared to control, 5FUBBR 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.

 Amaç: Bu çalışma, berberin BBR ile kemoterapinin omurgasını oluşturan 5-fluorourasil 5FUin 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 5FUnun 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. 5FUBBR, Bcl-2yi azaltarak ve p53ü 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, 5FUBBR 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, BBRnin 5FU ile birlikte kolorektal kanseri kemoterapisi için apoptoz indüksiyonu, inflamasyon baskılaması ve metastaz inhibisyonuyla muazzam potansiyelini ortaya koymaktadır.

Article Details

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

Authors:

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

Publisher:

Cukurova University

Main Topics:

Kanser Hücre Biyolojisi | Kemoterapi | Moleküler Hedefler

Journal:

Cukurova Medical Journal Vol.48 Issue 4, pp.1238-1247

Document Type:

Article

Publication Date:

12/2023

Document Language:

English

Document ID (Org No.):

2001286421

pISSN:

2602-3032

berberine (BBR)

5-fluorouracil (5FU)

synergism

Caco-2

apoptosis

MMP-9

Berberin (BBR)

5-fluorourasil (5FU)

sinerjizm

Caco-2

apoptosis

MMP-9

Issues

Article Details

Authors: Seyma Oncu | Merve Becit-kizilkaya | Serkan Şen | Fatma Özlem Kargın Solmaz | Sefa Çelik

Publisher: Cukurova University

Main Topics: Kanser Hücre Biyolojisi | Kemoterapi | Moleküler Hedefler

Journal: Cukurova Medical Journal Vol.48 Issue 4, pp.1238-1247

Document Type: Article

Publication Date: 12/2023

Document Language: English

Document ID (Org No.): 2001286421

pISSN: 2602-3032

Issues

Authors:

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

Publisher:

Cukurova University

Main Topics:

Kanser Hücre Biyolojisi | Kemoterapi | Moleküler Hedefler

Journal:

Cukurova Medical Journal Vol.48 Issue 4, pp.1238-1247

Document Type:

Article

Publication Date:

12/2023

Document Language:

English

Document ID (Org No.):

2001286421

pISSN:

2602-3032