Determination of the effects of fusaric acid, a mycotoxin, on cytotoxicity, gamma-H2AX, 8-hydroxy-2 deoxyguanosine and DNA repair gene in cancer cells

被引：6

作者：

Secme, Muecahit ^{[1
]}

Urganci, Aysen Buket Er ^{[2
]}

Uzen, Ramazan ^{[3
]}

Aslan, Ali ^{[4
]}

Tiras, Fatih ^{[5
]}

机构：

[1] Ordu Univ, Fac Med, Dept Med Biol, Ordu, Turkiye

[2] Pamukkale Univ, Fac Med, Dept Med Biol, Denizli, Turkiye

[3] Erciyes Univ, Fac Med, Dept Med Biol, Kayseri, Turkiye

[4] Ordu Univ, Fac Med, Dept Physiol, Ordu, Turkiye

[5] Dundee Univ, Leverhulme Res Ctr Forens Sci, Dundee, Scotland

来源：

TOXICON | 2023年 / 231卷

关键词：

Fusaric acid; PANC-1; MIA PaCa-2 cells; gamma-H2AX; 8-Hydroxy-2; desoxyguanosine; OXIDATIVE STRESS; APEX1; HEPG2;

D O I：

10.1016/j.toxicon.2023.107179

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

Pancreatic cancer has a poor prognosis and is an important public health problem for developing countries. Oxidative stress plays an important role in cancer initiation, progression, proliferation, invasion, angiogenesis and metastasis. For this reason, one of the important strategic targets of new cancer therapeutics is to drive cancer cells into apoptosis through oxidative stress. In nuclear and mitochondrial DNA, 8-hydroxy-2'-deoxyguanosine and gamma-H2AX (gamma-H2AX) are used as important oxidative stress biomarkers. Fusaric acid (FA) is a mycotoxin that mediates toxicity produced by Fusarium species and exhibits anticancer effects in various cancers via inducing apoptosis, cell cycle arrest, or other cellular mechanisms. The aim of this study was to determine the effects of fusaric acid on cytotoxic and oxidative damage in MIA PaCa-2 and PANC-1 cell lines. In this context, dose and time dependent cytotoxic effect of fusaric acid was determined by XTT method, mRNA expression levels of genes related to DNA repair were determined by RT-PCR, and its effect on 8-hydroxy-2'-deoxyguanosine and gamma-H2AX levels was revealed by ELISA assay. According to XTT results, fusaric acid inhibits cell proliferation in MIA PaCa-2 and Panc-1 cells in a dose- and time-dependent manner. IC50 doses were determined as 187.74 mu M at 48 h in MIA PaCa-2 cells and 134.83 mu M at 48 h in PANC-1 cells, respectively. gamma-H2AX and 8-OHdG changes were not found significant in pancreatic cancer cells. The mRNA expression levels of DNA repair-related genes NEIL1, OGG1, XRCC and Apex-1 change with exposure to fusaric acid. This study contributes to the therapeutic approaches to be developed for pancreatic cancer and demonstrates the potential of fusaric acid as an anticancer agent.

引用

页数：5

共 30 条

[21]

Mizrahi JD, 2020, LANCET, V395, P2008, DOI 10.1016/S0140-6736(20)30974-0

[22] Berzosertib (VE-822) inhibits gastric cancer cell proliferation via base excision repair system [J].