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Parvifloron D 对三阴性乳腺癌细胞的抗迁移和促凋亡作用。

Anti-Migratory and Pro-Apoptotic Properties of Parvifloron D on Triple-Negative Breast Cancer Cells.

机构信息

CBIOS, Universidade Lusófona Research Center for Biosciences & Health Technologies, Campo Grande 376, 1749-024 Lisboa, Portugal.

Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Av. Professor Gama Pinto, 1649-003 Lisboa, Portugal.

出版信息

Biomolecules. 2020 Jan 19;10(1):158. doi: 10.3390/biom10010158.

DOI:10.3390/biom10010158
PMID:31963771
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7023143/
Abstract

Medicinal plants are important sources of new bioactive compounds with potential anticancer activity. Parvifloron D (ParvD) is an abietane diterpenoid, isolated in high amounts from Benth. Previous reports have suggested potential therapeutic properties for ParvD. ParvD has shown pro-apoptotic and cytotoxic effects in leukemia and melanoma cell lines. However, to the best of our knowledge, there are no studies in triple-negative breast cancer (TNBC) models. TNBC is a breast cancer subtype characterized by an aggressive behavior with poor clinical outcomes and weak overall therapeutic responses to the current treatment options. This work aimed at evaluating the anticancer effect of ParvD in MDA-MB-231 cells, a model of human TNBC. To obtain sufficient amounts of purified ParvD the efficiency of several extraction methods was compared. ParvD (0.1-10 µM) decreased cell viability in a concentration-dependent manner. Treatment with ParvD (5 µM) significantly increased the percentage of apoptotic nuclei and exposure to 3 µM ParvD increased the sub-G1 population. Since altered cell adherence, migration, and invasion are determinant processes for the formation of metastases, the effect of ParvD on these cellular processes was tested. Although treatment with ParvD (1 µM) had no effect on cell-substrate attachment, ParvD (1 µM) significantly reduced cell chemotaxis and invasion. This is the first report describing the proapoptotic effect of ParvD in TNBC cells. Moreover, for the first time we have shown that ParvD reduces cell motility, unraveling potential anti-metastatic properties.

摘要

药用植物是具有潜在抗癌活性的新生物活性化合物的重要来源。Parvifloron D (ParvD) 是一种松香烷二萜,从 Benth 中大量分离得到。先前的报告表明 ParvD 具有潜在的治疗特性。ParvD 在白血病和黑色素瘤细胞系中表现出促凋亡和细胞毒性作用。然而,据我们所知,在三阴性乳腺癌 (TNBC) 模型中没有研究。TNBC 是一种乳腺癌亚型,其行为具有侵袭性,临床结局较差,对当前治疗选择的总体治疗反应较弱。这项工作旨在评估 ParvD 在 MDA-MB-231 细胞中的抗癌作用,MDA-MB-231 细胞是人类 TNBC 的模型。为了获得足够量的纯化 ParvD,比较了几种提取方法的效率。ParvD(0.1-10 µM)以浓度依赖的方式降低细胞活力。用 ParvD(5 µM)处理可显著增加凋亡核的百分比,而暴露于 3 µM ParvD 可增加亚 G1 群体。由于改变细胞黏附、迁移和侵袭是形成转移的决定因素,因此测试了 ParvD 对这些细胞过程的影响。尽管 ParvD(1 µM)处理对细胞-底物附着没有影响,但 ParvD(1 µM)显著降低了细胞趋化性和侵袭性。这是描述 ParvD 在 TNBC 细胞中促凋亡作用的首次报道。此外,我们首次表明 ParvD 降低了细胞迁移能力,揭示了潜在的抗转移特性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/06e6/7023143/f66b04166c64/biomolecules-10-00158-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/06e6/7023143/0bec9f0842cb/biomolecules-10-00158-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/06e6/7023143/c55e379ffae9/biomolecules-10-00158-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/06e6/7023143/d92e1cd65b1e/biomolecules-10-00158-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/06e6/7023143/318805d6fb14/biomolecules-10-00158-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/06e6/7023143/f66b04166c64/biomolecules-10-00158-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/06e6/7023143/0bec9f0842cb/biomolecules-10-00158-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/06e6/7023143/c55e379ffae9/biomolecules-10-00158-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/06e6/7023143/d92e1cd65b1e/biomolecules-10-00158-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/06e6/7023143/318805d6fb14/biomolecules-10-00158-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/06e6/7023143/f66b04166c64/biomolecules-10-00158-g005.jpg

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