Sophoraflavanone G suppresses the progression of triple-negative breast cancer via the inactivation of EGFR-PI3K-AKT signaling.

Abstract

Sophoraflavanone G (SG), a prenylated flavonoid extracted from Sophora flavescens, has been found to possess antitumor activity in several types of human cancer. However, the biological functions and molecular mechanism of SG in triple-negative breast cancer (TNBC) are required to be investigated. On the basis of network pharmacology methods and molecular docking technology, estimated glomerular filtration rate (EGFR) was identified as a potential target, and phosphatidylinositol 3-kinase-protein kinase B (PI3K-AKT) signaling was demonstrated as an important signaling pathway for SG to treat breast cancer. TNBC cells (BT-549 and MDA-MB-231) were used to determine the effects of SG in vitro. Cell Counting Kit, 5-ethynyl-2'-deoxyuridine, and colony formation assays confirmed the proliferation inhibition of SG on TNBC cells. Moreover, SG administration promoted cell apoptosis by affecting Bax, Bcl-2, and cleaved caspase-3 expression. SG treatment also enhanced oxidative stress of TNBC cells by inducing reactive oxygen species production, increasing malondialdehyde (MDA) level, and decreasing superoxide dismutase activity. Additionally, SG suppressed cell migration, invasion, and epithelial-mesenchymal transition process. Inactivated EGFR-PI3K-AKT signaling was observed in TNBC cells after treatment with SG. Furthermore, the inhibitory effects of SG on cell proliferation and metastasis and the promotive effects of SG on cell apoptosis and oxidative stress were significantly attenuated due to the overexpression of EGFR. Mice experiments revealed the suppression of SG on tumor growth and EGFR-PI3K-AKT signaling. Together, SG repressed the proliferation and metastasis, and induced apoptosis and oxidative stress in TNBC by targeting the EGFR-PI3K-AKT signaling pathway. SG might serve as a promising therapeutic agent to combat TNBC.

• Authors: Wei Cheng, Dan Liu, Min Guo, Honglei Li, Qiang Wang
• Journal: Drug development research (Drug Dev Res) Vol. 83 Issue 5 Pg. 1138-1151 (08 2022) ISSN: 1098-2299 [Electronic] United States
• PMID: 35426453 (Publication Type: Journal Article)
• Copyright: © 2022 Wiley Periodicals LLC.

Chemical References

• Flavanones
• vexibinol
• EGFR protein, human
• ErbB Receptors
• Proto-Oncogene Proteins c-akt

Topics

• Animals
• Apoptosis
• Cell Line, Tumor
• Cell Movement
• Cell Proliferation
• ErbB Receptors (metabolism, therapeutic use)
• Flavanones
• Glomerular Filtration Rate
• Humans
• Mice
• Molecular Docking Simulation
• Phosphatidylinositol 3-Kinases (metabolism)
• Proto-Oncogene Proteins c-akt (metabolism)
• Signal Transduction
• Triple Negative Breast Neoplasms (drug therapy, metabolism, pathology)