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体内研究新型色烯-4-酮衍生物作为 HCC 抗肿瘤剂

In vivo Study of a Newly Synthesized Chromen-4-one Derivative as an Antitumor Agent against HCC.

机构信息

Biochemistry Lab Chemistry Department Faculty of Education, Ain Shams University, Cairo, Egypt.

Department of Radiation Biology, National Center of Radiation Research and Technology, Atomic Energy Authority, Cairo, Egypt.

出版信息

J Gastrointest Cancer. 2022 Dec;53(4):980-989. doi: 10.1007/s12029-021-00724-9. Epub 2021 Oct 26.

DOI:10.1007/s12029-021-00724-9
PMID:34698995
Abstract

BACKGROUND

Chromenes are a wide group of natural compounds that can be synthesized chemically. The chromen-4-one nucleus acts as a skeleton for varieties of additional active groups that makes the chromene activity vary between antioxidant and anti-inflammatory agents. In the present study, a newly synthesized chromene compound exhibits different behaviors other than anti-inflammatory and antioxidant activities that it is the first time that a member of chromen-4-one compound can control the cancer progress. Inflammation is the first step in tumor development where the severity grade can potentiate tumor growth and progression. In many tumors, pro-inflammatory genes record high expression level such as tumor necrosis factor (TNF-α) and vascular endothelial growth factors (VEGF). These pro-inflammatory factors act as rate limiting steps in tumor initiation, and controlling its expression acts as an early therapeutic way to control the tumor proliferation. The chromone derivatives have biological activities such as anti-inflammatory and anti-tumor activity.

METHODS

In the present study, hepatocellular cancer (HCC) induced by diethylnitrosamine (DEN) in rats and then treated with the new chromene derivative and the parameters TNF-α, VEGF, p53, Cyt C, MMP-9, Bcl2, and Bax were measured.

RESULTS

The treatment strategy Ch compound is to downregulate pro-inflammatory gene expression of early genes as TNF-α as well as VEGF and subsequently control other factors such as p53, Cyt C, and MMP-9. Also, retrieve the balance between Bcl2 and Bax proteins in DEN-induced HCC in rats.

CONCLUSION

The ability of the new Ch derivative to control the primary initiators of HCC such as TNF-α offers this derivative an anti-tumor activity and encourages further researches to follow and monitor its effect on the molecular level.

摘要

背景

色烯是一大类天然化合物,可以通过化学合成得到。色烯-4-酮核作为各种附加活性基团的骨架,使色烯的活性在抗氧化剂和抗炎剂之间变化。在本研究中,一种新合成的色烯化合物表现出除抗炎和抗氧化活性以外的不同行为,这是首次发现色烯-4-酮化合物能够控制癌症进展。炎症是肿瘤发展的第一步,其严重程度可以增强肿瘤的生长和进展。在许多肿瘤中,促炎基因如肿瘤坏死因子(TNF-α)和血管内皮生长因子(VEGF)表达水平较高。这些促炎因子作为肿瘤起始的限速步骤,控制其表达是控制肿瘤增殖的早期治疗方法。色烯衍生物具有抗炎和抗肿瘤等生物活性。

方法

在本研究中,用二乙基亚硝胺(DEN)诱导大鼠肝细胞癌(HCC),然后用新的色烯衍生物治疗,并测量 TNF-α、VEGF、p53、Cyt C、MMP-9、Bcl2 和 Bax 等参数。

结果

Ch 化合物的治疗策略是下调 TNF-α等早期基因的促炎基因表达,从而控制 p53、Cyt C 和 MMP-9 等其他因子。此外,还恢复了 DEN 诱导的大鼠 HCC 中 Bcl2 和 Bax 蛋白之间的平衡。

结论

新型 Ch 衍生物能够控制 HCC 的主要启动子如 TNF-α,这使该衍生物具有抗肿瘤活性,并鼓励进一步研究跟踪并监测其在分子水平上的作用。

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