The Effect of 5-Florouracil and Resveratrol Combination on Apoptosis in A549 Human Lung Cancer Cell Line

Yıl 2019, , 359 - 368, 31.12.2019

Can Ali Ağca , Mahinur Kırıcı Abdurrahman Can Yeşim Yumak

https://doi.org/10.24938/kutfd.465470

Öz

Objective: 5-Fluorouracil (5-FU) is a
chemotherapy drug used in various cancers including breast, stomach, esophageal
and pancreatic cancer. Resveratrol (RES) is a well known non-flavon
polyphenolic compound that has chemotherapeutic effect in various types of
cancer. Despite the fact that effects of 5-FU and RES alone have been
extensively studied in the past few years, the effect of 5-FU combined with RES
in the A549 cell line remains unknown. In this study, we investigated the
effect of combination of RES and 5-FU on apoptotic pathway in A549 lung cancer
cell line.

Material and Methods: The effect of of 5-FU and
RES combination on A549 lung cancer cells was examined by cell viability using
Water Soluble Tetrazolium-1 (WST-1) assays, by ROS level using
2’,7’–dichlorofluorescin diacetate (DCFDA) assay and by the ability of
cells to form colonies by clonogenic assay, pro-apoptotic Bax and TIGAR protein
expression using Western Blotting analysis.

Results: Combination of 5-FU and
RES significantly
decreased cell viability and clonogenic potential of A549 cell line. Furthermore,
Western Blotting analysis showed that 5-FU and RES combination caused pro-apoptotic
Bax protein to increase, while TIGAR protein expression level decreased in
concentration-dependent manner.

Conclusion: Our results suggested that resveratrol
can increase the anti-tumor effect of 5-FU in A549 cell line.

Anahtar Kelimeler

5-Florouracil, Resveratrol, A549, TIGAR

5-FLOROURACİL VE RESVERATROL KOMBİNASYONUNUN İNSAN AKCİĞER KANSERİ A549 HÜCRE HATTINDA APOPTOZİS ÜZERİNE ETKİSİ

Öz

Amaç: 5-Florourasil
(5-FU), göğüs, mide, özofagus ve pankreas kanseri dahil olmak üzere çeşitli
kanser türlerinde kullanılan bir kemoterapi ilacıdır. Resveratrol (RES), flavon
olmayan polifenolik bir bileşiktir ve çeşitli kanser türlerinde kemoterapötik
etkisi bulunmaktadır. 5-FU ve RES'in etkilerinin
tek başına kapsamlı bir şekilde araştırılmasına rağmen, RES ile kombine edilen
5-FU'nun A549 hücre hattı üzerine etkisi hala bilinmemektedir. Bu çalışmada,
A549 akciğer kanseri hücre hattında 5-FU ve RES kombinasyonunun apopitotik
yolak üzerindeki etkisi araştırılmıştır.

Gereç ve
Yöntemler: 5-FU ve RES kombinasyonunun A549 akciğer kanseri
hücreleri üzerindeki etkisini belirlemek için, Water Soluble Tetrazolium-1
(WST-1) deneyi ile hücre canlılığı, 2’,7’–dichlorofluorescin diacetate (DCFDA) kiti
ile ROS seviyesi, klonojenik deney ile hücrelerin koloni oluşturma kabiliyeti,
Western blot ile pro-apoptotik Bax ve TP53
kaynaklı glikoliz ve apopitozis düzenleyicisi (TIGAR) proteinlerin ekspresyon
düzeyleri analiz edilmiştir.

Bulgular: 5-FU
ve RES kombinasyonu, A549 hücre hattının hücre canlılığını ve koloni oluşturma
potansiyelini önemli ölçüde azaltmıştır. Dahası, Western Blot analizi, 5-FU ve
RES kombinasyonunun pro-apopitotik Bax proteininin artmasına neden olduğunu,
TIGAR protein ekspresyon seviyesinin ise konsantrasyona bağlı bir şekilde
azaldığını göstermiştir.

Sonuç: Sonuçlarımız,
Resveratrolün A549 hücre dizisinde 5-FU'nun anti-tümör etkisini
artırabileceğini göstermiştir.

Anahtar Kelimeler

5-Florouracil, Resveratrol, A549, TIGAR

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