Transcriptomics analyses reveal the effects of Pentagamaboronon-0-ol on PI3K/Akt and cell cycle of HER2+ breast

Adam Hermawan1,2,3, Febri Wulandari2, Rohmad Yudi Utomo2,4

  • 1Laboratory of Macromolecular Engineering, Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Universitas Gadjah Mada Sekip Utara II, 55281, Yogyakarta, Indonesia.

Abstract

Insights

A curcumin analog, PGB-0-ol, shows cytotoxicity against HER2+ breast cancer cells. Next-generation sequencing revealed PGB-0-ol modulates PI3K/Akt signaling and cell cycle pathways, offering potential for new HER2-targeted therapies.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Targeted therapies and monoclonal antibodies have improved outcomes for HER2+ breast cancer but drug resistance necessitates novel treatments.
  • A curcumin analog, PGB-0-ol, exhibits significant cytotoxicity against HCC1954 HER2+ breast cancer cells.

Purpose of the Study:

  • To elucidate the molecular mechanisms of PGB-0-ol action in HER2+ breast cancer cells using next-generation sequencing.
  • To identify key signaling pathways and biological processes affected by PGB-0-ol treatment.

Main Methods:

  • Next-generation sequencing (NGS) to analyze transcriptomic changes in HCC1954 cells treated with PGB-0-ol.
  • Bioinformatics analyses including Gene Ontology (GO), KEGG pathway, disease-gene, drug-gene associations, Network Topology Analysis (NTA), and Gene Set Enrichment Analysis (GSEA).

Main Results:

  • Identified 2,263 differentially expressed genes (DEGs) in PGB-0-ol-treated cells.
  • KEGG analysis indicated modulation of phosphatidylinositol and ErbB signaling pathways.
  • GO and GSEA revealed impacts on cell cycle, mitotic spindle, nuclear membrane, and kinase activity, specifically implicating PI3K/Akt signaling and cell cycle regulation.

Conclusions:

  • PGB-0-ol treatment alters the transcriptomic profile of HER2+ breast cancer cells.
  • Bioinformatics analyses suggest PGB-0-ol modulates PI3K/Akt signaling and cell cycle pathways.
  • Further research is needed to validate these findings and explore PGB-0-ol as a potential therapeutic agent.

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