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

Adam Hermawan; Febri Wulandari; Rohmad Yudi Utomo; Ratna Asmah Susidarti; Mitsunori Kirihata; Edy Meiyanto

doi:10.1016/j.jsps.2023.101847

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

Saudi Pharm J. 2023 Dec;31(12):101847. doi: 10.1016/j.jsps.2023.101847. Epub 2023 Oct 27.

Authors

Adam Hermawan^{1

2

3}, Febri Wulandari², Rohmad Yudi Utomo^{2

4}, Ratna Asmah Susidarti^{2

4}, Mitsunori Kirihata⁵, Edy Meiyanto^{1

2}

Affiliations

¹ Laboratory of Macromolecular Engineering, Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Universitas Gadjah Mada Sekip Utara II, 55281, Yogyakarta, Indonesia.
² Cancer Chemoprevention Research Center, Faculty of Pharmacy, Universitas Gadjah Mada Sekip Utara II, 55281, Yogyakarta, Indonesia.
³ Laboratory of Advanced Pharmaceutical Sciences. APSLC Building, Faculty of Pharmacy, Universitas Gadjah Mada Sekip Utara II, 55281, Yogyakarta, Indonesia.
⁴ Laboratory of Medicinal Chemistry, Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Universitas Gadjah Mada Sekip Utara II, 55281, Yogyakarta, Indonesia.
⁵ Research Center for BNCT, Osaka Metropolitan University, 1-2, Gakuen-cho, Naka-ku, Sakai, Osaka 599-8570, Japan.

Abstract

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.

Keywords: Anticancer; Drug development; HER2+ breast cancer; PGB-0-ol; Transcriptomics.