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

Hermawan, Adam and Wulandari, Febri and Yudi Utomo, Rohmad and Asmah Susidarti, Ratna and Kirihata, Mitsunori and Meiyanto, Edy (2023) Transcriptomics analyses reveal the effects of Pentagamaboronon-0-ol on PI3K/Akt and cell cycle of HER2+ breast cancer cells. Saudi Pharmaceutical Journal, 31 (12). ISSN 13190164

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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. © 2023 The Author(s)

Item Type: Article
Additional Information: Cited by: 1; All Open Access, Gold Open Access, Green Open Access
Uncontrolled Keywords: 26S proteasome non ATPase regulatory subunit 2; 5' amp activated protein kinase catalytic subunit alpha 1; acyl protein thioesterase 1; alpha2 integrin; alpha6 integrin; atpase 13a3; beta6 integrin; BRCA1 protein; cadherin 1; curcumin; cyclic AMP responsive element binding protein 3 like protein 4; cytotoxic agent; endoplasmic reticulum metallopeptidase 1; epidermal growth factor receptor; epidermal growth factor receptor 2; eukaryotic translation initiation factor 3 subunit C like protein; excitatory amino acid transporter 1; exportin T; focal adhesion kinase 1; hexokinase 2; isoleucine transfer RNA ligase; Janus kinase 2; laminin subunit alpha 3; lim domain and actin binding protein 1; macrophage colony stimulating factor 1; nuclear fragile X mental retardation interacting protein 2; pentagamaboronon 0 ol; phosphatidylinositol 3 kinase; phosphatidylinositol 4,5 bisphosphate 3 kinase catalytic subunit beta; phosphoinositide dependent protein kinase 1; phosphotransferase; platelet activating factor acetylhydrolase IB subunit beta; protein; protein kinase B; raf proto oncogene serine threonineprotein kinase; scatter factor receptor; serine threonine protein kinase n2; serine threonine protein phosphatase 2A 56 kDa regulatory subunit epsilon isoform; solute carrier family 6A member 6; STAT3 protein; syntenin; tuberin; unclassified drug; yes proto oncogene 1; Article; bioinformatics; cell cycle regulation; cell nucleus membrane; controlled study; cytotoxicity; differential gene expression; down regulation; enzyme activity; gene; gene ontology; gene set enrichment analysis; HCC1954 cell line; high throughput sequencing; human epidermal growth factor receptor 2 positive breast cancer; KEGG; mitosis spindle; Pi3K/Akt signaling; transcriptomics; upregulation
Subjects: R Medicine > RS Pharmacy and materia medica
Divisions: Faculty of Pharmacy
Depositing User: Sri JUNANDI
Date Deposited: 30 Oct 2024 13:05
Last Modified: 30 Oct 2024 13:05
URI: https://ir.lib.ugm.ac.id/id/eprint/6015

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