Salinomycin inhibits breast cancer progression via targeting HIF-1α/VEGF mediated tumor angiogenesis in vitro and in vivo.

Abstract

Cancer is a complex disease wherein cells begin to divideabnormally and spread into surrounding tissues. Angiogenesis plays a crucial role in tumor progression as it is required for sustained growth and metastasis, therefore targeting angiogenesis is a promising therapeutic approach for breast cancer management. Salinomycin (SAL) has been reported to exhibit anticancer response on various types of cancer. In the present study, we explored the antiangiogenic and anticancer efficacy of the polyether ionophore SAL in the breast cancer model. It effectively inhibited cell proliferation, invasion, and migration. It also inhibited the expression of pro-angiogenic cell surface marker CD31 in HUVEC, thereby interrupting the endothelial tubulogenesis. It decreased the HIF-1α transcription factor DNA binding activity to HRE sequence in HUVEC and human breast cancer cells. Further, corresponding to our in vitro findings, SAL suppressed neovascularization in the chick chorioallantoic membrane and the Matrigel plug implanted mice model. Bioluminescence and immunofluorescence imaging revealed that SAL treatment in mice inhibits breast cancer growth and tumor angiogenesis. SAL also suppressed the serum VEGFA level in tumor-bearing mice and induced caspase-dependent apoptosis in breast cancer cells. Taken together our findings suggested that SAL inhibits VEGF induced angiogenesis and breast cancer growth via interrupting HIF-1α/VEGF signalling and could be used as a promising antiangiogenic agent for breast cancer treatment.

• Authors: Jayant Dewangan, Sonal Srivastava, Sakshi Mishra, Aman Divakar, Sadan Kumar, Srikanta Kumar Rath
• Journal: Biochemical pharmacology (Biochem Pharmacol) Vol. 164 Pg. 326-335 (06 2019) ISSN: 1873-2968 [Electronic] England
• PMID: 31028743 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2019 Elsevier Inc. All rights reserved.

Chemical References

• Angiogenesis Inhibitors
• HIF1A protein, human
• Hypoxia-Inducible Factor 1, alpha Subunit
• Pyrans
• VEGFA protein, human
• Vascular Endothelial Growth Factor A
• salinomycin

Topics

• Angiogenesis Inhibitors (administration & dosage)
• Animals
• Breast Neoplasms (drug therapy, metabolism, pathology)
• Chick Embryo
• Disease Progression
• Dose-Response Relationship, Drug
• Drug Delivery Systems (methods)
• Female
• HEK293 Cells
• Human Umbilical Vein Endothelial Cells (drug effects, metabolism)
• Humans
• Hypoxia-Inducible Factor 1, alpha Subunit (antagonists & inhibitors, metabolism)
• MCF-7 Cells
• Mice
• Mice, Inbred BALB C
• Pyrans (administration & dosage)
• Tumor Burden (drug effects, physiology)
• Vascular Endothelial Growth Factor A (antagonists & inhibitors, metabolism)