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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.
Introduction:
Monoclonal antibodies and targeted therapies against HER2+ breast cancer has improved overall and disease-free survival in patients; however, encountering drug resistance causes recurrence, necessitating the development of newer HER2-targeted medications. A curcumin analog PGB-0-ol showed most cytotoxicity against HCC1954 HER2+ breast cancer cells than against other subtypes of breast cancer cells.
Objective:
Here, we employed next-generation sequencing technology to elucidate the molecular mechanism underlying the effect of PGB-0-ol on HCC1954 HER2+ breast cancer cells.
Methods:
The molecular mechanism underlying the action of PGB-0-ol on HCC1954 HER2+ breast cancer cells was determined using next-generation sequencing technologies. Additional bioinformatics studies were performed, including gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, disease-gene, and drug-gene associations, network topology analysis (NTA), and gene set enrichment analysis (GSEA).
Results:
We detected 2,263 differentially expressed genes (DEGs) (1,459 upregulated and 804 downregulated) in the PGB-0-ol- and DMSO-treated HCC1954 cells. KEGG enrichment data revealed the control of phosphatidylinositol signaling system, and ErbB signaling following PGB-0-ol treatment. Gene ontology (GO) enrichment analysis demonstrated that these DEGs governed cell cycle, participated in the mitotic spindle and nuclear membrane, and controlled kinase activity at the molecular level. According to the NTA data for GO enrichment, GSEA data for KEGG, drug-gene and disease-gene, PGB-0-ol regulated PI3K/Akt signaling and cell cycle in breast cancer. Overall, our investigation revealed the transcriptomic profile of PGB-0-ol-treated HCC1954 breast cancer cells following PGB-0-ol therapy. Bioinformatics analyses showed that PI3K/Akt signaling and cell cycle was modulated. However, further studies are required to validate the findings of this study.
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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