Anti-cancer activity of synthetic gefitinib-1,2,3-triazole derivatives against Hela cells via induction of apoptosis.

IF 4.2 3区 化学 Q2 CHEMISTRY, MULTIDISCIPLINARY Frontiers in Chemistry Pub Date : 2025-01-24 eCollection Date: 2025-01-01 DOI:10.3389/fchem.2025.1456743
Zhihong Hu, Xixi Hou, Yongjing Ren, Ziyuan Wu, Dong Yan, Hong Chen, Lan Wang
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Abstract

Cervical cancer ranks as the fourth most common cancer among women. However, the current treatments have significant side effects and limited therapeutic effects on advanced diseases, so it is necessary to discover better treatments for cervical cancer. The current study investigated the potential anticancer effects of a series of gefitinib-1,2,3-triazole derivative on Hela cells. Among the investigated, the target compound c13 showed good anticancer activity against Hela cells (IC50 = 5.66 ± 0.35 μM) compared with gefitinib (IC50 = 14.18 ± 3.19 μM). Moreover, compound c13 significantly inhibited the colony formation ability of Hela cells in a dose-dependent manner, accompanied by morphological changes in HeLa cells. Further investigations demonstrated that compound c13 triggered cell apoptosis and arrested the cell cycle at the G2/M phase in Hela cells. In addition, western blot analysis revealed that compound c13 upregulated the Bax/Bcl-2 ratio, and increased the levels of active caspase 3 and PARP1 cleavage, which suggested the involvement of the mitochondrial pathway in compound c13-induced apoptosis. In brief, these results indicated that compound c13 is a promising compound for the treatment of cervical cancer.

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合成吉非替尼-1,2,3-三唑衍生物诱导Hela细胞凋亡的抗癌活性
子宫颈癌是女性中第四大常见癌症。然而,目前的治疗方法副作用明显,对晚期疾病的治疗效果有限,因此有必要发现更好的宫颈癌治疗方法。本研究探讨了一系列吉非替尼-1,2,3-三唑衍生物对Hela细胞的潜在抗癌作用。其中,目标化合物c13对Hela细胞的IC50值为5.66±0.35 μM,优于吉非替尼(IC50值为14.18±3.19 μM)。化合物c13显著抑制Hela细胞集落形成能力,且呈剂量依赖性,并伴有Hela细胞形态改变。进一步研究表明,化合物c13可触发Hela细胞的细胞凋亡,使细胞周期停留在G2/M期。此外,western blot分析显示,化合物c13上调Bax/Bcl-2比值,增加活性caspase 3和PARP1切割水平,提示化合物c13介导的细胞凋亡可能与线粒体通路有关。总之,这些结果表明化合物c13是一种很有前景的治疗宫颈癌的化合物。
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来源期刊
Frontiers in Chemistry
Frontiers in Chemistry Chemistry-General Chemistry
CiteScore
8.50
自引率
3.60%
发文量
1540
审稿时长
12 weeks
期刊介绍: Frontiers in Chemistry is a high visiblity and quality journal, publishing rigorously peer-reviewed research across the chemical sciences. Field Chief Editor Steve Suib at the University of Connecticut is supported by an outstanding Editorial Board of international researchers. This multidisciplinary open-access journal is at the forefront of disseminating and communicating scientific knowledge and impactful discoveries to academics, industry leaders and the public worldwide. Chemistry is a branch of science that is linked to all other main fields of research. The omnipresence of Chemistry is apparent in our everyday lives from the electronic devices that we all use to communicate, to foods we eat, to our health and well-being, to the different forms of energy that we use. While there are many subtopics and specialties of Chemistry, the fundamental link in all these areas is how atoms, ions, and molecules come together and come apart in what some have come to call the “dance of life”. All specialty sections of Frontiers in Chemistry are open-access with the goal of publishing outstanding research publications, review articles, commentaries, and ideas about various aspects of Chemistry. The past forms of publication often have specific subdisciplines, most commonly of analytical, inorganic, organic and physical chemistries, but these days those lines and boxes are quite blurry and the silos of those disciplines appear to be eroding. Chemistry is important to both fundamental and applied areas of research and manufacturing, and indeed the outlines of academic versus industrial research are also often artificial. Collaborative research across all specialty areas of Chemistry is highly encouraged and supported as we move forward. These are exciting times and the field of Chemistry is an important and significant contributor to our collective knowledge.
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