Transcriptomics and Proteomics Characterizing the Anticancer Mechanisms of Natural Rebeccamycin Analog Loonamycin in

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Clinicopathological Analysis of miRNA Expression in Breast Cancer Tissues by Using miRNA In Situ Hybridization
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Clinicopathological Analysis of miRNA Expression in Breast Cancer Tissues by Using miRNA In Situ Hybridization

Published on: June 7, 2016

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Xiao Sun1, Zhanying Lu1, Zhenzhen Liang2

  • 1Experimental Training Center of Basic Medical Science, College of Basic Medical Sciences, Naval Medical University, Shanghai 200433, China.

Molecules (Basel, Switzerland)
|October 27, 2022
PubMed

Insights

Loonamycin (LM) demonstrates anticancer effects against triple-negative breast cancer by inducing apoptosis and inhibiting tumor growth. Its mechanism involves targeting topoisomerase I and the p53 and EGFR/PI3K/AKT/mTOR signaling pathways.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Triple-negative breast cancer (TNBC) remains a challenging subtype with limited targeted therapies.
  • Identifying novel therapeutic agents with distinct mechanisms of action is crucial for improving patient outcomes.

Purpose of the Study:

  • To investigate the anticancer potential of loonamycin (LM) against TNBC.
  • To elucidate the molecular mechanisms underlying LM's therapeutic effects using multi-omics approaches.

Main Methods:

  • In vitro assays assessing cytotoxicity and apoptosis induction in human TNBC cells.
  • In vivo studies utilizing a murine xenograft model to evaluate LM's tumor inhibitory effects.
  • Combined transcriptomics, proteomics, and Gene Set Enrichment Analysis (GSEA) to identify affected pathways.

Main Results:

  • LM exhibited significant anticancer activity in vitro by promoting apoptosis in TNBC cells.
  • LM administration effectively inhibited MDA-MB-468 tumor growth in a murine xenograft model.
  • Mechanistic studies revealed LM inhibits topoisomerase I and impacts O-glycan, p53, and EGFR/PI3K/AKT/mTOR signaling pathways.

Conclusions:

  • Loonamycin demonstrates promising anticancer efficacy against triple-negative breast cancer.
  • LM's mechanism of action involves topoisomerase I inhibition and modulation of critical signaling pathways including p53 and EGFR/PI3K/AKT/mTOR.
Keywords:
O-glycanPI3K/AKT/mTORloonamycinp53triple negative breast cancer

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