富含芪类化合物的提取物增强了紫杉醇对激素受体阳性和三阴性乳腺癌球体的细胞毒性作用。

Stilbene-rich extract increases the cytotoxic effects of paclitaxel in hormone receptor-positive and triple-negative breast cancer spheroids.

作者信息

Mohammadhosseinpour Sepideh, Weaver Alexx, Hernandez-Madrigal Sara V, Gajurel Gaurav, Sharma Amit Raj, Medina-Bolivar Fabricio

机构信息

Molecular Biosciences Graduate Program, Arkansas State University, Jonesboro, AR 72401, United States.

Arkansas Biosciences Institute, Arkansas State University, Jonesboro, AR 72401, United States.

出版信息

Phytomed Plus. 2024 Aug;4(3). doi: 10.1016/j.phyplu.2024.100578. Epub 2024 May 13.

DOI:10.1016/j.phyplu.2024.100578

PMID:39574482

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11580422/

Abstract

BACKGROUND

Triple-negative breast cancer (TNBC) is an aggressive form of breast cancer that lacks three receptors commonly found in breast cancer cells. It is associated with high mortality rates, and therefore, investigating therapies to increase survival rates is crucial. Plant-derived compounds are being explored as potential adjuvants for common chemotherapy drugs, such as paclitaxel (Pac).

PURPOSE

The study aimed to evaluate the cytotoxic effect of a prenylated stilbene-rich extract (SRE) produced via a sustainable peanut hairy root culture system and observe its potential as an adjuvant for Pac in human triple-negative and hormone receptor-positive (HR+) breast cancer spheroids. The effects were compared to arachidin-1 (A-1), a cytotoxic prenylated stilbene present in the extract.

METHODS

SRE was produced from elicited peanut hairy root cultures. The extract was purified using chromatography techniques to obtain the prenylated stilbene arachidin-1 (A-1) with a purity of over 95 %. TNBC cell lines MDA-MB-231, MDA-MB-436, and HR+ breast cancer cell line MCF-7 were used to evaluate the cytotoxicity and apoptotic activity of SRE in comparison with A-1. Two-dimensional (2D) experiments were performed using cell viability assays and imaging microscopy. Three-dimensional (3D) spheroids cultures were established, and the impact of SRE alone and in combination with Pac on cell viability and caspase 3/7 activity was evaluated.

RESULTS

SRE (10 μg/mL) inhibited cell proliferation by approximately 50 % in TNBC and MCF-7 cells in a time-dependent manner. Additionally, Annexin V FITC/PI staining revealed that SRE (10 μg/mL) induced more apoptosis than A-1 at the equimolar concentration (5 μM) in MDA-MB-231 cells. Combining SRE with Pac decreased spheroid cell viability and induced apoptosis by activating caspases 3 and 7 in TNBC and HR+ breast cancer spheroids.

CONCLUSIONS

These findings highlight the potential of SRE as a novel adjuvant for Pac chemotherapy in TNBC and HR+ breast cancer treatment.

摘要

背景

三阴性乳腺癌（TNBC）是一种侵袭性乳腺癌，缺乏乳腺癌细胞中常见的三种受体。它与高死亡率相关，因此，研究提高生存率的治疗方法至关重要。植物来源的化合物正在被探索作为常见化疗药物如紫杉醇（Pac）的潜在佐剂。

目的

本研究旨在评估通过可持续花生毛状根培养系统生产的富含异戊烯基化芪的提取物（SRE）的细胞毒性作用，并观察其作为Pac佐剂在人三阴性和激素受体阳性（HR+）乳腺癌球体中的潜力。将这些作用与提取物中存在的细胞毒性异戊烯基化芪花生四烯酸-1（A-1）进行比较。

方法

SRE由诱导的花生毛状根培养物产生。提取物通过色谱技术纯化，以获得纯度超过95%的异戊烯基化芪花生四烯酸-1（A-1）。使用三阴性乳腺癌细胞系MDA-MB-231、MDA-MB-436和激素受体阳性乳腺癌细胞系MCF-7来评估SRE与A-1相比的细胞毒性和凋亡活性。使用细胞活力测定和成像显微镜进行二维（2D）实验。建立三维（3D）球体培养，并评估单独使用SRE以及与Pac联合使用对细胞活力和半胱天冬酶3/7活性的影响。

结果

SRE（10μg/mL）以时间依赖性方式抑制TNBC和MCF-7细胞的增殖约50%。此外，膜联蛋白V FITC/PI染色显示，在MDA-MB-231细胞中，SRE（10μg/mL）在等摩尔浓度（5μM）下比A-1诱导更多的凋亡。将SRE与Pac联合使用可降低TNBC和HR+乳腺癌球体中的球体细胞活力，并通过激活半胱天冬酶3和7诱导凋亡。