Rhein Derivative 4F Inhibits the Malignant Phenotype of Breast Cancer by Downregulating Rac1 Protein

Triple-negative breast cancer is a common malignant tumor with unfavorable prognosis affecting women worldwide; thus, there is an urgent need for novel therapeutic drugs with improved anti-tumor activity. Rac family small GTPase 1 (Rac1) plays an important role in malignant behavior and is a promisi...

Full description

Saved in:
Bibliographic Details
Published in:Frontiers in pharmacology 2020-05, Vol.11, p.754-754
Main Authors: Li, Xinxiao, Liu, Yunfeng, Zhao, Yuhua, Tian, Wei, Zhai, Lina, Pang, Huifeng, Kang, Jiankang, Hou, Huaxin, Chen, Yanhua, Li, Danrong
Format: Article
Language:English
Subjects:
anticancer
breast cancer
drug design
Pharmacology
Rac family small GTPase 1
Rhein derivative
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Triple-negative breast cancer is a common malignant tumor with unfavorable prognosis affecting women worldwide; thus, there is an urgent need for novel therapeutic drugs with improved anti-tumor activity. Rac family small GTPase 1 (Rac1) plays an important role in malignant behavior and is a promising therapeutic target. We reported an anthraquinone compound, Rhein, and its derivative, 4F, and investigated their downregulation effects on Rac1 in breast cancer cells . The inhibition of cell proliferation by derivative 4F was investigated in two breast cancer (MDA-MB-231 and MCF-7) and normal breast (MCF-10A) cell lines by cell counting kit-8 assay and growth curves. The role of 4F in cell migration and invasion and cytoskeletal change were assessed by Transwell chamber assay and F-actin staining, respectively. The affinity of Rhein and its derivative for Rac1 protein and the regulation of Rac1 promoter activity were evaluated by molecular docking software and luciferase reporter gene assay, respectively. Rac1 protein expression was determined by western blot assay. Compared to Rhein, derivative 4F more strongly inhibited breast cancer cell proliferation, migration, and invasion and also cause cytoskeletal changes like those in paclitaxel. Derivative 4F not only bound more stably to Rac1 but also inhibited Rac1 promoter activity in cells and downregulated Rac1 protein expression. Rhein derivative 4F is a new anthraquinone compound with better anti-tumor activity than that of the lead compound Rhein in breast cancer. It down-regulated Rac1 expression and may be a small molecule inhibitor of Rac1.
ISSN:1663-9812
1663-9812
DOI:10.3389/fphar.2020.00754