文献检索文档翻译深度研究
Suppr Zotero 插件Zotero 插件
邀请有礼套餐&价格历史记录

新学期，新优惠

限时优惠:9月1日-9月22日

30天高级会员仅需29元

1天体验卡首发特惠仅需5.99元

了解详情
不再提醒
插件&应用
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
高级版
套餐订阅购买积分包
AI 工具
文献检索文档翻译深度研究
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利：CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2025

橙皮素通过网络药理学和分子对接促进膀胱癌细胞死亡的 PI3K/AKT 通路。

Hesperetin promotes bladder cancer cells death via the PI3K/AKT pathway by network pharmacology and molecular docking.

机构信息

Department of Urology, The First Affiliated Hospital of Harbin Medical University, 23 Postal Street, Harbin, 150000, Heilongjiang, China.

Key Laboratory of Hepatosplenic Surgery, Ministry of Education, The First Affiliated Hospital of Harbin Medical University, Harbin, 150000, Heilongjiang, China.

出版信息

Sci Rep. 2024 Jan 10;14(1):1009. doi: 10.1038/s41598-023-50476-8.

DOI:10.1038/s41598-023-50476-8
PMID:38200039
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10781778/
Abstract

Patients with bladder cancer (BLCA) still show high recurrence after surgery and chemotherapy. Hesperetin (HE), as a natural compound, has attracted researchers' attention due to its low toxicity and easy access. However, the inhibitory effect of HE on BLCA remains unknown. The hub genes and enrichment pathways regulated by HE in the treatment of BLCA were predicted by network pharmacology. The molecular docking of HE and hub proteins was visualized. Colony and CCK8 assays were used to test cell proliferation, and BLCA migration was confirmed by transwell and wound healing assays. In addition, the occurrence of apoptosis and ferroptosis was demonstrated by Hoechst staining, transmission electron microscopy (TEM) and ROS (reactive oxygen species) assay. Western Blotting was performed to validate the hub proteins, target functions and pathways. SRC, PIK3R1 and MAPK1 were identified as hub targets for HE in BLCA, involving the PI3k/AKT pathway. Furthermore, HE inhibited the proliferation and migration of BLCA cells. The MMP2/MMP9 proteins were significantly inhibited by HE. The increased expression of Bax and cleaved caspase-3 indicated that HE could promote BLCA cell apoptosis. In addition, Hoechst staining revealed concentrated and illuminated apoptotic nuclei. The activation of ROS and the decline of GPX4 expression suggested that HE might induce ferroptosis as an anti-BLCA process. Shrunk mitochondria and apoptotic bodies were observed in BLCA cells treated with HE, with reduced or absent mitochondrial cristae. We propose for the first time that HE could inhibit the proliferation and migration of BLCA cells and promote apoptosis and ferroptosis. HE may act by targeting proteins such as SRC, PIK3R1 and MAPK1 and the PI3K/AKT pathway.

摘要

患有膀胱癌 (BLCA) 的患者在手术后和化疗后仍表现出高复发率。橙皮素 (HE) 作为一种天然化合物，由于其低毒性和易得性，引起了研究人员的关注。然而，HE 对 BLCA 的抑制作用尚不清楚。通过网络药理学预测 HE 治疗 BLCA 调节的枢纽基因和富集途径。可视化 HE 和枢纽蛋白的分子对接。使用集落和 CCK8 测定法测试细胞增殖，通过 Transwell 和划痕愈合测定法证实 BLCA 迁移。此外，通过 Hoechst 染色、透射电子显微镜 (TEM) 和 ROS (活性氧) 测定法证明细胞凋亡和铁死亡的发生。通过 Western Blotting 验证枢纽蛋白、靶功能和途径。SRC、PIK3R1 和 MAPK1 被确定为 HE 在 BLCA 中的枢纽靶标，涉及 PI3k/AKT 途径。此外，HE 抑制 BLCA 细胞的增殖和迁移。HE 显著抑制 MMP2/MMP9 蛋白。Bax 和 cleaved caspase-3 的表达增加表明 HE 可以促进 BLCA 细胞凋亡。此外，Hoechst 染色显示凋亡核浓缩和发光。ROS 的激活和 GPX4 表达的下降表明 HE 可能作为抗 BLCA 过程诱导铁死亡。用 HE 处理的 BLCA 细胞中观察到线粒体收缩和凋亡小体，线粒体嵴减少或消失。我们首次提出，HE 可以抑制 BLCA 细胞的增殖和迁移，促进细胞凋亡和铁死亡。HE 可能通过靶向 SRC、PIK3R1 和 MAPK1 等蛋白以及 PI3K/AKT 途径发挥作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f0c3/10781778/76ea44f0f505/41598_2023_50476_Fig13_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f0c3/10781778/75c2b6906754/41598_2023_50476_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f0c3/10781778/9f753fa21046/41598_2023_50476_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f0c3/10781778/fdfe24f29581/41598_2023_50476_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f0c3/10781778/989a206be4b3/41598_2023_50476_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f0c3/10781778/f08c08a93a17/41598_2023_50476_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f0c3/10781778/80bc9ecc9cdc/41598_2023_50476_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f0c3/10781778/8e3dbccfbdf5/41598_2023_50476_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f0c3/10781778/9e213f580a8e/41598_2023_50476_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f0c3/10781778/2b7e191b6b7a/41598_2023_50476_Fig9_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f0c3/10781778/42b54f6ca502/41598_2023_50476_Fig10_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f0c3/10781778/e22f776757a8/41598_2023_50476_Fig11_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f0c3/10781778/1be5ce52b84c/41598_2023_50476_Fig12_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f0c3/10781778/76ea44f0f505/41598_2023_50476_Fig13_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f0c3/10781778/75c2b6906754/41598_2023_50476_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f0c3/10781778/9f753fa21046/41598_2023_50476_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f0c3/10781778/fdfe24f29581/41598_2023_50476_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f0c3/10781778/989a206be4b3/41598_2023_50476_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f0c3/10781778/f08c08a93a17/41598_2023_50476_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f0c3/10781778/80bc9ecc9cdc/41598_2023_50476_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f0c3/10781778/8e3dbccfbdf5/41598_2023_50476_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f0c3/10781778/9e213f580a8e/41598_2023_50476_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f0c3/10781778/2b7e191b6b7a/41598_2023_50476_Fig9_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f0c3/10781778/42b54f6ca502/41598_2023_50476_Fig10_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f0c3/10781778/e22f776757a8/41598_2023_50476_Fig11_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f0c3/10781778/1be5ce52b84c/41598_2023_50476_Fig12_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f0c3/10781778/76ea44f0f505/41598_2023_50476_Fig13_HTML.jpg

相似文献

[1]
Hesperetin promotes bladder cancer cells death via the PI3K/AKT pathway by network pharmacology and molecular docking.

Sci Rep. 2024-1-10

[2]
Hesperetin Inhibits Bladder Cancer Cell Proliferation and Promotes Apoptosis and Cycle Arrest by PI3K/AKT/FoxO3a and ER Stress-mitochondria Pathways.

Curr Med Chem. 2024-2-13

[3]
A network pharmacology approach and experimental validation to investigate the anticancer mechanism and potential active targets of ethanol extract of Wei-Tong-Xin against colorectal cancer through induction of apoptosis via PI3K/AKT signaling pathway.

J Ethnopharmacol. 2023-3-1

[4]
TEAD4 functions as a prognostic biomarker and triggers EMT via PI3K/AKT pathway in bladder cancer.

J Exp Clin Cancer Res. 2022-5-17

[5]
Network pharmacology and in vitro experiments reveal sophoridine-induced apoptosis and G phase arrest via ROS-dependent PI3K/Akt/FoxO3a pathway activation in human bladder cancer cells.

Chem Biol Drug Des. 2024-2

[6]
The Role of Emodin in the Treatment of Bladder Cancer Based on Network Pharmacology and Experimental Verification.

Comb Chem High Throughput Screen. 2024

[7]
Potential mechanisms of osthole against bladder cancer cells based on network pharmacology, molecular docking, and experimental validation.

BMC Complement Med Ther. 2023-4-17

[8]
Bupivacaine modulates the apoptosis and ferroptosis in bladder cancer via phosphatidylinositol 3-kinase (PI3K)/AKT pathway.

Bioengineered. 2022-3

[9]
The Prognostic Hub Gene POLE2 Promotes BLCA Cell Growth via the PI3K/AKT Signaling Pathway.

Comb Chem High Throughput Screen. 2024

[10]
WITHDRAWN: Network Pharmacology and In vitro Experiments Reveal that Noscapine Induces Ros-mediated Apoptosis and Cell Cycle Arrest via PI3K/Akt/FoxO3a Signaling Pathway in Human Bladder Cancer Cells.

Curr Cancer Drug Targets. 2025-1-7

引用本文的文献

[1]
Food-derived compounds targeting ferroptosis for cancer therapy: from effects to mechanisms.

Front Oncol. 2025-6-9

[2]
Bee Pollen Potential to Modulate Ferroptosis: Phytochemical Insights for Age-Related Diseases.

Antioxidants (Basel). 2025-2-25

[3]
Plant Secondary Metabolites as Modulators of Mitochondrial Health: An Overview of Their Anti-Oxidant, Anti-Apoptotic, and Mitophagic Mechanisms.

Int J Mol Sci. 2025-1-4

[4]
Bioactive Compounds in Peel Are Potential Candidates for Alleviating Physical Fatigue through a Triad Approach of Network Pharmacology, Molecular Docking, and Molecular Dynamics Modeling.

Nutrients. 2024-6-18

本文引用的文献

[1]
Hesperetin Inhibits TGF-β1-Induced Migration and Invasion of Triple Negative Breast Cancer MDA-MB-231 Cells via Suppressing Fyn/Paxillin/RhoA Pathway.

Integr Cancer Ther. 2022

[2]
Ferroptosis in cancer therapy: a novel approach to reversing drug resistance.

Mol Cancer. 2022-2-12

[3]
Chemotherapeutic potential of hesperetin for cancer treatment, with mechanistic insights: A comprehensive review.

Heliyon. 2022-1-23

[4]
Roles of ferroptosis in urologic malignancies.

Cancer Cell Int. 2021-12-18

[5]
Application of nanotechnology in the diagnosis and treatment of bladder cancer.

J Nanobiotechnology. 2021-11-27

[6]
Natural Phytochemicals in Bladder Cancer Prevention and Therapy.

Front Oncol. 2021-4-30

[7]
Multi-omics reveals novel prognostic implication of SRC protein expression in bladder cancer and its correlation with immunotherapy response.

Ann Med. 2021-12

[8]
Hesperetin promotes DOT1L degradation and reduces histone H3K79 methylation to inhibit gastric cancer metastasis.

Phytomedicine. 2021-4

[9]
Quercetin induces p53-independent cancer cell death through lysosome activation by the transcription factor EB and Reactive Oxygen Species-dependent ferroptosis.

Br J Pharmacol. 2021-3

[10]
Advances in bladder cancer biology and therapy.

Nat Rev Cancer. 2021-2

文献AI研究员

20分钟写一篇综述，助力文献阅读效率提升50倍

立即体验

用中文搜PubMed

大模型驱动的PubMed中文搜索引擎

马上搜索

推荐工具

医学文档翻译智能文献检索