Cytotoxic and Apoptotic Effects of Propolis Combined with 5-Fluorouracil in HCT-116 Cells

Ayşe Çekin; Latife Merve Oktay Çelebi; Burak Durmaz; Eser Y. Sözmen; Nur Selvi Günel

doi:10.19161/etd.1860820

EN TR

Cytotoxic and Apoptotic Effects of Propolis Combined with 5-Fluorouracil in HCT-116 Cells

Abstract

Colon cancer is the third leading cause of cancer-related mortality worldwide and the most common malignancy of the gastrointestinal tract. The primary chemotherapeutic agent used in colon cancer is 5-Fluorouracil (5-FU), a fluoropyrimidine antimetabolite that inhibits DNA synthesis by arresting cells in the S phase of the cell cycle. Despite its widespread use, overall survival rates with 5-FU therapy remain limited, necessitating combination approaches to enhance its efficacy. Propolis is a natural product that has gained scientific attention due to its anti-inflammatory, antibacterial, and antioxidant properties. Ethanol-based propolis extracts are the most commonly used due to their high extraction efficiency. Combining chemotherapeutic agents with natural compounds has been proposed as a strategy to improve treatment outcomes. However, to date, no study has been found investigating the combination of 5-FU with Turkish propolis specifically in HCT-116 cells. In this study, we evaluated the cytotoxic, apoptotic, and cell cycle effects of combined 5-FU and Turkish propolis treatment in HCT-116 colon cancer cells, using untreated cells as controls. Optimal cell density was determined by a proliferation assay, and cytotoxicity was assessed by MTT analysis. Combination treatments were applied based on IC50 values, and apoptosis was analyzed using Annexin V-FITC flow cytometry. The IC50 values at 72 hours were 407.7 μg/mL for propolis and 9.5 μM for 5-FU. At this time point, the combination treatment induced G2/M phase arrest and a significant reduction in S phase. Overall, these findings suggest that combining propolis with 5-FU may enhance anticancer efficacy and support future in vivo and clinical studies.

Keywords

HCT-116 Hücrelerinde 5-Florourasil ve Propolis Kombinasyonunun Sitotoksik ve Apoptotik Etkileri

Abstract

Kolon kanseri, dünya çapında kansere bağlı ölümlerin üçüncü önde gelen nedenidir ve gastrointestinal sistemin en yaygın malignitesidir. Kolon kanserinde kullanılan birincil kemoterapötik ajan, hücre döngüsünün S fazında hücreleri durdurarak DNA sentezini inhibe eden bir floropirimidin antimetaboliti olan 5-Fluorouracil'dir (5-FU). Yaygın kullanımına rağmen, 5-FU tedavisi ile genel sağkalım oranları sınırlı kalmaktadır ve etkinliğini artırmak için kombinasyon yaklaşımlarını gerektirmektedir. Propolis, anti-enflamatuar, antibakteriyel ve antioksidan özellikleri nedeniyle bilimsel ilgi gören doğal bir üründür. Etanol bazlı propolis özütleri, yüksek ekstraksiyon verimliliği nedeniyle en yaygın kullanılanlardır. Kemoterapötik ajanların doğal bileşiklerle birleştirilmesi, tedavi sonuçlarını iyileştirmek için bir strateji olarak önerilmiştir. Bununla birlikte, bugüne kadar, özellikle HCT-116 hücrelerinde 5-FU'nun Türk propolisi ile kombinasyonunu araştıran hiçbir çalışma bulunamamıştır. Bu çalışmada, HCT-116 kolon kanseri hücrelerinde kombine 5-FU ve Türk propolisinin sitotoksik, apoptotik ve hücre döngüsü etkileri, kontrol grubu olarak tedavi edilmemiş hücreler kullanılarak değerlendirilmiştir. Optimal hücre yoğunluğu, proliferasyon testi ile belirlenmiş ve sitotoksisite MTT analizi ile değerlendirilmiştir. Kombine tedaviler IC50 değerlerine göre uygulanmış ve apoptoz, Annexin V-FITC akış sitometrisi kullanılarak analiz edilmiştir. 72 saatteki IC50 değerleri propolis için 407,7 μg/mL ve 5-FU için 9,5 μM olarak bulunmuştur. Bu zaman noktasında, kombine tedavi G2/M fazında duraklamaya ve S fazında önemli bir azalmaya neden olmuştur. Genel olarak, bu bulgular propolisin 5-FU ile kombinasyonunun antikanser etkinliğini artırabileceğini ve gelecekteki in vivo ve klinik çalışmaları destekleyebileceğini göstermektedir.

Keywords

Supporting Institution

This study was funded by the Scientific Research Projects Coordination Office of Ege University (EGE BAP-Project No: TYL-2021-23026).

Project Number

EGE BAP: TYL-2021-23026

Ethical Statement

This article does not contain any studies with human participants or animals performed by any of the authors.

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Details

Primary Language

English

Subjects

Clinical Sciences (Other)

Journal Section

Research Article

Authors

Ayşe Çekin ^*
0000-0002-7442-4661
Türkiye

Latife Merve Oktay Çelebi
0000-0002-7110-3379
Türkiye

Burak Durmaz
0000-0002-5285-3641
Türkiye

Eser Y. Sözmen
0000-0002-6383-6724
Türkiye

Nur Selvi Günel
0000-0003-0612-2263
Türkiye

Publication Date

June 10, 2026

Submission Date

January 23, 2026

Acceptance Date

February 12, 2026

Published in Issue

Year 2026 Volume: 65 Number: 2

DOI

https://doi.org/10.19161/etd.1860820

IZ

https://izlik.org/JA87EZ47ET

Cite

RIS / Bibtex

APA

Çekin, A., Oktay Çelebi, L. M., Durmaz, B., Y. Sözmen, E., & Selvi Günel, N. (2026). Cytotoxic and Apoptotic Effects of Propolis Combined with 5-Fluorouracil in HCT-116 Cells. Ege Tıp Dergisi, 65(2), 283-294. https://doi.org/10.19161/etd.1860820

AMA

1.Çekin A, Oktay Çelebi LM, Durmaz B, Y. Sözmen E, Selvi Günel N. Cytotoxic and Apoptotic Effects of Propolis Combined with 5-Fluorouracil in HCT-116 Cells. EJM. 2026;65(2):283-294. doi:10.19161/etd.1860820

Chicago

Çekin, Ayşe, Latife Merve Oktay Çelebi, Burak Durmaz, Eser Y. Sözmen, and Nur Selvi Günel. 2026. “Cytotoxic and Apoptotic Effects of Propolis Combined With 5-Fluorouracil in HCT-116 Cells”. Ege Tıp Dergisi 65 (2): 283-94. https://doi.org/10.19161/etd.1860820.

EndNote

Çekin A, Oktay Çelebi LM, Durmaz B, Y. Sözmen E, Selvi Günel N (June 1, 2026) Cytotoxic and Apoptotic Effects of Propolis Combined with 5-Fluorouracil in HCT-116 Cells. Ege Tıp Dergisi 65 2 283–294.

IEEE

[1]A. Çekin, L. M. Oktay Çelebi, B. Durmaz, E. Y. Sözmen, and N. Selvi Günel, “Cytotoxic and Apoptotic Effects of Propolis Combined with 5-Fluorouracil in HCT-116 Cells”, EJM, vol. 65, no. 2, pp. 283–294, June 2026, doi: 10.19161/etd.1860820.

ISNAD

Çekin, Ayşe - Oktay Çelebi, Latife Merve - Durmaz, Burak - Y. Sözmen, Eser - Selvi Günel, Nur. “Cytotoxic and Apoptotic Effects of Propolis Combined With 5-Fluorouracil in HCT-116 Cells”. Ege Tıp Dergisi 65/2 (June 1, 2026): 283-294. https://doi.org/10.19161/etd.1860820.

JAMA

1.Çekin A, Oktay Çelebi LM, Durmaz B, Y. Sözmen E, Selvi Günel N. Cytotoxic and Apoptotic Effects of Propolis Combined with 5-Fluorouracil in HCT-116 Cells. EJM. 2026;65:283–294.

MLA

Çekin, Ayşe, et al. “Cytotoxic and Apoptotic Effects of Propolis Combined With 5-Fluorouracil in HCT-116 Cells”. Ege Tıp Dergisi, vol. 65, no. 2, June 2026, pp. 283-94, doi:10.19161/etd.1860820.

Vancouver

1.Ayşe Çekin, Latife Merve Oktay Çelebi, Burak Durmaz, Eser Y. Sözmen, Nur Selvi Günel. Cytotoxic and Apoptotic Effects of Propolis Combined with 5-Fluorouracil in HCT-116 Cells. EJM. 2026 Jun. 1;65(2):283-94. doi:10.19161/etd.1860820