Ginsenoside Rh1 Prevents Migration and Invasion through Mitochondrial ROS-Mediated Inhibition of STAT3/NF-κB Signaling in MDA-MB-231 Cells

• Published in: International journal of molecular sciences Vol. 22; no. 19; p. 10458
• Main Authors: Jin, Yujin, Huynh, Diem Thi Ngoc, Myung, Chang-Seon, Heo, Kyung-Sun
• Format: Journal Article
• Language: English
• Published: Basel MDPI AG 01-10-2021; MDPI
• Subjects: Angiogenesis; Apoptosis; Breast cancer; Cell adhesion & migration; Cytokines; Gelatinase A; Gelatinase B; ginsenoside Rh1; Inflammation; Kinases; Liver cancer; Metastases; Metastasis; Mitochondria; mitochondrial ROS; Morphology; Mutation; NF-κB; NF-κB protein; Phosphorylation; Protein expression; Proteins; Signal transduction; STAT3; Stat3 protein; Transcription; triple-negative breast cancer cells; Tumorigenesis; Vascular endothelial growth factor; Western blotting; Wound healing
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms221910458

Breast cancer (BC) a very common cancer in women worldwide. Triple negative breast cancer (TNBC) has been shown to have a poor prognosis with a high level of tumor metastatic spread. Here, the inhibitory effects of ginsenoside-Rh1 (Rh1) on BC metastasis, and its underlying signaling pathway in TNBC were investigated. Rh1-treated MDA-MB-231 cells were analyzed for metastasis using a wound healing assay, transwell migration and invasion assay, western blotting, and qRT-PCR. Rh1 treatment significantly inhibited BC metastasis by inhibiting the both protein and mRNA levels of MMP2, MMP9, and VEGF-A. Further, Rh1-mediated inhibitory effect on BC migration was associated with mitochondrial ROS generation. Rh1 treatment significantly eliminated STAT3 phosphorylation and NF-κB transactivation to downregulate metastatic factors, such as MMP2, MMP9, and VEGF-A. In addition, Mito-TEMPO treatment reversed Rh1 effects on the activation of STAT3, NF-κB, and their transcriptional targets. Rh1 further enhanced the inhibitory effects of STAT3 or NF-κB specific inhibitor, stattic or BAY 11-7082 on MMP2, MMP9, and VEGF-A expression, respectively. In summary, our results revealed the potent anticancer effect of Rh1 on TNBC migration and invasion through mtROS-mediated inhibition of STAT3 and NF-κB signaling.