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来自葡萄藤的1,3,5-三咖啡酰奎尼酸诱导卵巢癌细胞凋亡并抑制内皮管形成。

1,3,5-Tricaffeoylquinic Acid from Vines Induced Ovarian Cancer Cell Apoptosis and Inhibited Endothelial Tube Formation.

作者信息

Lee Dahae, Kim Jaekyoung, Baek Soyoon, Lee Jin Woo, Lee Changyeol, Kang Ki Sung, Shim Sang Hee

机构信息

College of Korean Medicine, Gachon University, Seongnam 13120, Republic of Korea.

Natural Products Research Institute, College of Pharmacy, Seoul National University, Seoul 08826, Republic of Korea.

出版信息

Biomol Ther (Seoul). 2025 May 1;33(3):483-493. doi: 10.4062/biomolther.2024.239. Epub 2025 Apr 8.

DOI:10.4062/biomolther.2024.239
PMID:40195283
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12059361/
Abstract

Ovarian cancer usually metastasizes from the ovary to adjacent organs through direct invasion with blood vessels formed by endothelial cells. Targeting apoptosis of ovarian cancer and angiogenesis is promising for anticancer therapy. Leaves of sp. have reportedly shown promise in treating ovarian cancer. Here, we investigated the apoptosis-inducing and anti-angiogenic effects of compounds isolated from vines (IBV). Phytochemical examination of IBV led to the isolation and verification of eight compounds (): chlorogenic acid (), 3,4-dicaffeoylquinic acid (), 3,5-dicaffeoylquinic acid (), 4,5-dicaffeoylquinic acid (), 1,3,5-tricaffeoylquinic acid (), -feruloyltyramine (), scopoletin (), and esculetin (). Of these, 1,3,5-tricaffeoylquinic acid (5) showed the highest cytotoxicity in A2780 human ovarian cancer cells, inducing apoptotic death in more than 37% cells and decreasing viability to less than 25% at 100 μM. Compound increased the levels of cleaved caspase-8, Bax, cleaved PARP, and caspase-3/9, and decreased the levels of cleaved Bcl-2. Further, inhibited tubule formation in HUVECs. VEGFR2, ERK, PI3K, Akt, and mTOR protein expression was also suppressed by . Then, a simple, rapid, and reliable LC-MS/ MS method was developed to determine the contents of the isolated compounds from IBV. Overall, has potential for treating ovarian cancer as it induces apoptosis in ovarian cancer cells and inhibits tube formation.

摘要

卵巢癌通常通过由内皮细胞形成的血管直接侵袭，从卵巢转移至邻近器官。靶向卵巢癌的凋亡和血管生成在抗癌治疗中具有前景。据报道，某植物的叶子在治疗卵巢癌方面显示出前景。在此，我们研究了从该植物藤蔓中分离出的化合物（IBV）的诱导凋亡和抗血管生成作用。对IBV进行植物化学分析，导致分离并鉴定出8种化合物（）：绿原酸（）、3,4 - 二咖啡酰奎宁酸（）、3,5 - 二咖啡酰奎宁酸（）、4,5 - 二咖啡酰奎宁酸（）、1,3,5 - 三咖啡酰奎宁酸（）、对香豆酰酪胺（）、东莨菪素（）和七叶亭（）。其中，1,3,5 - 三咖啡酰奎宁酸（5）在A2780人卵巢癌细胞中显示出最高的细胞毒性，在100μM时诱导超过37%的细胞凋亡死亡，并使细胞活力降低至低于25%。化合物5增加了裂解的半胱天冬酶 - 8、Bax、裂解的PARP和半胱天冬酶 - 3/9的水平，并降低了裂解的Bcl - 2的水平。此外，5抑制了人脐静脉内皮细胞（HUVECs）中的小管形成。5还抑制了VEGFR2、ERK、PI3K、Akt和mTOR蛋白的表达。然后，开发了一种简单、快速且可靠的液相色谱 - 串联质谱（LC - MS/MS）方法来测定从IBV中分离出的化合物的含量。总体而言，IBV具有治疗卵巢癌的潜力，因为它能诱导卵巢癌细胞凋亡并抑制小管形成。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2f3e/12059361/1ea59af4c879/bt-33-3-483-f8.jpg
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