Salidroside inhibits migration, invasion and angiogenesis of MDA‑MB 231 TNBC cells by regulating EGFR/Jak2/STAT3 signaling via MMP2.

Abstract

The major hallmarks of tumor progression are angiogenesis, migration and metastasis. Among the components of Rhodiola rosea, salidroside (p‑hydroxyphenethyl-β‑d-glucoside) is one of the most potent, and is present in all Rhodiola species. Recent data have revealed the anticancer effects of salidroside; however, the mechanism underlying its ability to inhibit tumor angiogenesis remains unknown. The present study aimed to analyze how salidroside affects major factors involved in breast cancer, and to elucidate its ability to inhibit angiogenesis and invasion. Signal transducer and activator of transcription 3 (STAT3) is a marker for tumor angiogenesis and migration, which interacts with matrix metalloproteinases (MMPs). Specifically, MMPs act as a downstream target for STAT3. Using western blotting and reverse transcription-quantitative polymerase chain reaction analysis, the present study demonstrated that treatment of MDA‑MB 231 triple-negative breast cancer (TNBC) cells with salidroside led to inhibition of invasion and migration markers, and of STAT3 signaling. Furthermore, in vitro angiogenesis analyses in human umbilical vein endothelial cells confirmed the anti-angiogenic activity of salidroside. An electrophoretic mobility shift assay also demonstrated that salidroside may inhibit the DNA-binding activity of STAT3, preventing STAT3 from binding to a novel binding site of the MMP2 gene promoter. In conclusion, the present results demonstrated that salidroside may downregulate the STAT3 signaling pathway, and inhibit cell viability, migration and invasion through MMPs in breast cancer cells.

• Authors: Dong Young Kang, Nipin Sp, Doh Hoon Kim, Youn Hee Joung, Hyo Gun Lee, Young Min Park, Young Mok Yang
• Journal: International journal of oncology (Int J Oncol) Vol. 53 Issue 2 Pg. 877-885 (Aug 2018) ISSN: 1791-2423 [Electronic] Greece
• PMID: 29901185 (Publication Type: Journal Article)

Chemical References

• Angiogenesis Inhibitors
• Antineoplastic Agents, Phytogenic
• Glucosides
• Phenols
• STAT3 Transcription Factor
• STAT3 protein, human
• EGFR protein, human
• ErbB Receptors
• JAK2 protein, human
• Janus Kinase 2
• MMP2 protein, human
• Matrix Metalloproteinase 2
• rhodioloside

Topics

• Angiogenesis Inhibitors (pharmacology)
• Antineoplastic Agents, Phytogenic (pharmacology)
• Cell Line, Tumor
• Cell Movement (drug effects)
• Cell Survival (drug effects)
• ErbB Receptors (genetics, metabolism)
• Female
• Gene Expression Regulation, Neoplastic (drug effects)
• Glucosides (pharmacology)
• Humans
• Janus Kinase 2 (genetics, metabolism)
• Matrix Metalloproteinase 2 (genetics, metabolism)
• Neoplasm Invasiveness
• Phenols (pharmacology)
• STAT3 Transcription Factor (genetics, metabolism)
• Signal Transduction (drug effects)
• Triple Negative Breast Neoplasms (drug therapy, genetics, metabolism)