NMR 分析鉴定出针对西妥昔单抗耐药结肠癌细胞系的细胞毒性化合物。

NMR Profiling of Identifies Cytotoxic Compounds against Cetuximab-Resistant Colon Cancer Cell Lines.

机构信息

Dipartimento di Scienze e Tecnologie Ambientali, Biologiche e Farmaceutiche, Università degli Studi della Campania "Luigi Vanvitelli", Via Vivaldi 43, 81100 Caserta, Italy.

Oncologia medica, Dipartimento di Medicina di precisione, Università degli Studi della Campania "Luigi Vanvitelli", S. Andrea delle Dame, Via L. De Crecchio 7, 80138 Napoli, Italy.

出版信息

Molecules. 2021 May 28;26(11):3266. doi: 10.3390/molecules26113266.

DOI:10.3390/molecules26113266

PMID:34071597

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8198399/

Abstract

In the search of new natural products to be explored as possible anticancer drugs, two plant species, namely and , were screened against colorectal cancer cell lines. The cytotoxic activity of the crude extracts was tested on a panel of colon cancer cell models including cetuximab-sensitive (Caco-2, GEO, SW48), intrinsic (HT-29 and HCT-116), and acquired (GEO-CR, SW48-CR) cetuximab-resistant cell lines. showed remarkable cytotoxic activity, especially on the cetuximab-resistant cell lines. The active extract composition was determined by NMR analysis. Given its complexity, a partial purification was then carried out. The fractions obtained were again tested for their biological activity and their metabolite content was determined by 1D and 2D NMR analysis. The study led to the identification of a fraction enriched in oxylipins that showed a 92% growth inhibition of the HT-29 cell line at a concentration of 50 µg/mL.

摘要

在寻找新的天然产物作为可能的抗癌药物的过程中，对两种植物物种，即和，进行了筛选，以对抗结直肠癌细胞系。对包括西妥昔单抗敏感（Caco-2、GEO、SW48）、固有（HT-29 和 HCT-116）和获得（GEO-CR、SW48-CR）西妥昔单抗耐药细胞系在内的一组结肠癌模型进行了粗提取物的细胞毒性测试。表现出显著的细胞毒性活性，尤其是对西妥昔单抗耐药细胞系。通过 NMR 分析确定了活性提取物的组成。由于其复杂性，然后进行了部分纯化。再次测试获得的馏分的生物活性，并通过 1D 和 2D NMR 分析确定其代谢产物含量。该研究导致鉴定出一种富含氧化脂类的馏分，该馏分在 50 µg/mL 浓度下对 HT-29 细胞系的生长抑制率达到 92%。