Dual anti-angiogenic and anti-metastatic activity of myriocin synergistically enhances the anti-tumor activity of cisplatin

Ji Hak Jeong, Uttam Ojha, Hyeonha Jang, Soohyun Kang, Sunhee Lee, You Mie Lee

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Purpose: Tumor microenvironment consists of various kind of cells, forming complex interactions and signal transductions for tumor growth. Due to this complexity, targeting multiple kinases could yield improved clinical outcomes. In this study, we aimed to investigate the potential of myriocin, from Mycelia sterilia, as a novel dual-kinase inhibitor and suggest myriocin as a candidate for combined chemotherapy. Methods: We initially evaluated the anti-tumor and anti-metastatic effect of myriocin in mouse allograft tumor models. We examined the effects of myriocin on angiogenesis and tumor vasculature using in vitro, in vivo, and ex vivo models, and also tested the anti-migration effect of myriocin in in vitro models. Next, we explored the effects of myriocin alone and in combination with cisplatin on tumor growth and vascular normalization in mouse models. Results: We found that myriocin inhibited tumor growth and lung metastasis in mouse allograft tumor models. Myriocin induced normalization of the tumor vasculature in the mouse models. We also found that myriocin suppressed angiogenesis through the VEGFR2/PI3K/AKT pathway in endothelial cells (ECs), as well as cancer cell migration by blocking the IκBα/NF-κB(p65)/MMP-9 pathway. Finally, we found that myriocin enhanced the drug delivery efficacy of cisplatin by increasing the integrity of tumor vasculature in the mouse models, which synergistically increased the anti-tumor activity of cisplatin. Conclusion: We suggest that myriocin is a novel potent anti-cancer agent that dually targets both VEGFR2 in ECs and IκBα in cancer cells, and exerts more pronounced anti-tumor effects than with either kinase being inhibited alone.

Original languageEnglish
Pages (from-to)117-132
Number of pages16
JournalCellular oncology (Dordrecht)
Volume46
Issue number1
DOIs
StatePublished - Feb 2023

Keywords

  • IκBα/NF-κB
  • MMP-9
  • Myriocin
  • Tumor vascular normalization
  • VEGFR2

Fingerprint

Dive into the research topics of 'Dual anti-angiogenic and anti-metastatic activity of myriocin synergistically enhances the anti-tumor activity of cisplatin'. Together they form a unique fingerprint.

Cite this