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一种通过靶向作用揭示芦丁(生物类黄酮)在宫颈癌细胞中凋亡潜能的新方法。

A Novel Approach to Unraveling the Apoptotic Potential of Rutin (Bioflavonoid) via Targeting in Cervical Cancer Cells.

机构信息

Department of Biotechnology, Noida Institute of Engineering and Technology, Greater Noida 201306, India.

Department of Biochemistry, Faculty of Science, Embryonic Stem Cells Unit, King Abdulaziz University, Jeddah 21589, Saudi Arabia.

出版信息

Molecules. 2021 Sep 12;26(18):5529. doi: 10.3390/molecules26185529.

Abstract

Rutin has been well recognized for possessing numerous pharmacological and biological activities in several human cancer cells. This research has addressed the inhibitory potential of rutin against the oncogene in SiHa cancer cells, which is known to inactivate various tumor suppressor proteins including and . Further, the inhibitory efficacy of rutin via expression modulation in cervical cancer has not been yet elucidated. Hence, we hypothesized that rutin could exhibit strong inhibitory efficacy against and, thereby, induce significant growth arrest in SiHa cancer cells in a dose-dependent manner. In our study, the cytotoxic efficacy of rutin on the proliferation of a cervical cancer cell line (SiHa) was exhibited using MTT and LDH assays. The correlation between rutin and mRNA expression was assessed by RT-PCR analysis and the associated events (a mechanism) with this downregulation were then explored via performing ROS assay, DAPI analysis, and expression analysis of apoptosis-associated signaling molecules such as , , and and -9 using qRT-PCR analysis. Results exhibit that rutin produces anticancer effects via inducing modulation in the expression of oncogenes as well as tumor suppressor genes. Further apoptosis induction, caspase activation, and ROS generation in rutin-treated SiHa cancer cells explain the cascade of events associated with downregulation in SiHa cancer cells. Additionally, apoptosis induction was further confirmed by the FITC-Annexin V/PI double staining method. Altogether, our research supports the feasibility of developing rutin as one of the potent drug candidates in cervical cancer management via targeting one such crucial oncogene associated with cervical cancer progression.

摘要

芦丁已被广泛认可,具有多种在人类癌细胞中的药理和生物学活性。本研究探讨了芦丁对 SiHa 癌细胞致癌基因的抑制潜力,该基因已知能使多种肿瘤抑制蛋白失活,包括 和 。此外,芦丁通过调节 表达在宫颈癌中的抑制作用尚未阐明。因此,我们假设芦丁可以对 和 表现出很强的抑制作用,从而以剂量依赖的方式诱导 SiHa 癌细胞的显著生长停滞。在我们的研究中,MTT 和 LDH 测定法显示芦丁对宫颈癌细胞系(SiHa)增殖的细胞毒性作用。通过 RT-PCR 分析评估芦丁与 mRNA 表达之间的相关性,然后通过进行 ROS 测定、DAPI 分析以及使用 qRT-PCR 分析凋亡相关信号分子如 、 、 和 -9 的表达分析来探索与这种下调相关的相关事件(一种机制)。结果表明,芦丁通过诱导致癌基因和肿瘤抑制基因表达的调节产生抗癌作用。芦丁处理的 SiHa 癌细胞中的凋亡诱导、半胱天冬酶激活和 ROS 产生解释了与 SiHa 癌细胞中 下调相关的级联事件。此外,通过 FITC-Annexin V/PI 双重染色法进一步证实了凋亡诱导。总之,我们的研究支持通过靶向与宫颈癌进展相关的一个关键致癌基因,将芦丁开发为宫颈癌管理中一种潜在药物候选物的可行性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/045f/8472561/db286248db8d/molecules-26-05529-g001.jpg

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