通过靶向乳腺癌 Notch 信号研究香芹酚的抗癌潜力

IF 2.1 4区 化学 Q3 CHEMISTRY, MULTIDISCIPLINARY Open Chemistry Pub Date : 2024-04-03 DOI:10.1515/chem-2024-0008
Pratibha Pandey, Seema Ramniwas, Meenakshi Verma, Nishesh Sharma, Vijay Jagdish Upadhye, Fahad Khan, Mohd Asif Shah
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引用次数: 0

摘要

乳腺癌(BC)仍然是全球关注的主要健康问题,尽管人们已经做出巨大努力,采用新型化疗技术来治疗乳腺癌。因此,有必要针对各种癌症细胞类型中失调的信号传导成分,阐明更好的植物化合物。我们的目标是通过采用硅和体外方法,利用香芹酚在 MDA-MB-231 细胞中的抗癌潜力,阐明一种有效的靶向治疗方法。我们进行了硅学分析,以确定香芹酚通过靶向NOTCH通路的关键信号成分(即Jagged-1及其下游靶点细胞周期蛋白D1)对BC的抗癌潜力。体外试验也显示了香芹酚通过靶向Jagged-1和细胞周期蛋白D1基因在MDA-MB-231细胞mRNA水平上的抗增殖潜力。使用 CB DOCK 进行的对接研究显示,与标准药物 5-氟尿嘧啶(Jagged-1:-4.5;cyclin D1:-4.6)相比,香芹酚(Jagged-1:-5.0;cyclin D1:-5.8)与这些关键靶点的结合能更高。香芹酚可能会下调这些关键基因的表达,同时诱导由 Caspase 介导的细胞凋亡。然而,要验证香芹酚是否可用于开发抗癌药物,还必须采用更多的体外检测方法。这项研究为利用天然产品和失调的信号传导成分来治疗乳腺癌提供了一种新的靶向治疗方法。
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A study to investigate the anticancer potential of carvacrol via targeting Notch signaling in breast cancer
Breast cancer (BC) continues to be a primary worldwide health concern despite the tremendous efforts made to deploy novel chemotherapeutic techniques for the treatment of BC. It is, therefore, essential to elucidate better plant-based compounds targeting deregulated signaling components in various cancer cell types. Our objective was to elucidate a potent targeted therapeutic approach by exploiting the anticancerous potential of carvacrol in MDA-MB-231 cells via employing silicon and in vitro approaches. In silico analysis was executed to identify the anticancer potential of carvacrol against BC via targeting crucial signaling component of the NOTCH pathway, namely Jagged-1 and its downstream target cyclin D1. In vitro, assays were also employed to display the antiproliferative potential of carvacrol at the mRNA level in MDA-MB-231 cells via targeting Jagged-1 and cyclin D1 genes. Docking studies using CB DOCK displayed better binding energy of carvacrol (Jagged-1: −5.0 and cyclin D1: −5.8) in comparison to the standard drug, 5-fluorouracil (Jagged-1: −4.5; cyclin D1: −4.6) against these crucial targets. Carvacrol potentially downregulated the expression of these crucial genes along with caspase-mediated apoptosis induction. However, more in vitro assays must be employed to validate its candidature for drug development against BC. This study provided a novel insight into the targeted therapeutic approach using natural products and deregulated signaling components for managing breast carcinoma.
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来源期刊
Open Chemistry
Open Chemistry CHEMISTRY, MULTIDISCIPLINARY-
CiteScore
3.80
自引率
4.30%
发文量
90
审稿时长
6 weeks
期刊介绍: Open Chemistry is a peer-reviewed, open access journal that publishes original research, reviews and short communications in the fields of chemistry in an ongoing way. The central goal is to provide a hub for researchers working across all subjects to present their discoveries, and to be a forum for the discussion of the important issues in the field. The journal is the premier source for cutting edge research in fundamental chemistry and it provides high quality peer review services for its authors across the world. Moreover, it allows for libraries everywhere to avoid subscribing to multiple local publications, and to receive instead all the necessary chemistry research from a single source available to the entire scientific community.
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