Liquid chromatography–high-resolution mass spectrometry-based metabolomics revealing the effects of zearalenone and alpha-zearalenol on human endometrial cancer cells

代谢组学 化学 玉米赤霉烯酮 克隆形成试验 代谢物 细胞生长 生物化学 真菌毒素 生物 细胞 色谱法 食品科学
作者
Marhaba Marhaba,Narendra Kumar Nagendla,Saria Anjum,Sireesha Ganneru,Varsha Singh,Saurabh Pal,Mohana Krishna Reddy Mudiam,Kausar M. Ansari
出处
期刊:Toxicology Research [Oxford University Press]
卷期号:13 (5): tfae169-tfae169
标识
DOI:10.1093/toxres/tfae169
摘要

Abstract Human exposure to mycotoxins through food involve a mixture of compounds, which can be harmful to human health. The Fusarium fungal species are known to produce zearalenone (ZEN), a non-steroidal estrogenic mycotoxin, and its metabolite alpha-zearalenol (α-ZEL), both of which possess endocrine-disruptive properties. Given their potential harm to human health through food exposure, investigating the combined effects of ZEN and α-ZEL becomes crucial. Hence, the combined impact of ZEN and α-ZEL study hold significant importance. This in vitro study delves into the critical area, examining their combined impact on the proliferation and metabolic profile of endometrial cancer Ishikawa cells via sulforhodamine, clonogenic, proliferating cell nuclear antigen (PCNA) and liquid chromatography-high resolution mass spectrometry (LC-HRMS) based untargeted metabolomics. Low concentrations of ZEN (25 nm), α-ZEL (10 nm), or a combination of both were observed to significantly enhance cell proliferation of Ishikawa cells, as evidenced by PCNA immunostaining, immunoblotting as well and clonogenic assays. The metabolomics revealed the perturbations in glycerophospholipid metabolism, nicotinate and nicotinamide metabolism and phenylalanine, tyrosine, tryptophan biosynthesis provides valuable insights into potential mechanism by which these mycotoxins may facilitate cell proliferation. However, further investigations are warranted to comprehensively understand the implications of these findings and their possible implications for human health.
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