Integrated transcriptome and in vitro analysis revealed anti-proliferative effect of sodium perborate on hepatocellular carcinoma cells

• Published in: Journal of trace elements in medicine and biology Vol. 73; p. 127011
• Main Authors: Omeroglu Ulu, Zehra, Bolat, Zeynep Busra, Sahin, Fikrettin
• Format: Journal Article
• Language: English
• Published: Elsevier GmbH 01.09.2022
• Subjects: Anti-cancer therapy; Hepatocellular carcinoma; Sodium perborate tetrahydrate; Transcriptome analysis; Hepatocellular carcinoma; Transcriptome analysis; Sodium perborate tetrahydrate; Anti-cancer therapy
• ISSN: 0946-672X; 1878-3252
• DOI: 10.1016/j.jtemb.2022.127011

Hepatocelular carcinoma is one of the leading cancer types with no effective cure as poor prognosis is still a challenging aspect. Thus, alternative therapeutics are necessary to control hepatocelular carcinoma. Boron derivatives such as boric acid (BA), sodium perborate tetrahydrate (SPT) and sodium pentaborate pentahydrate (NaB) have been discovered to have anti-cancer effect. This study investigated the anti-proliferative effects of SPT against hepatocelular carcinoma (HCC) using in vitro and transcriptome approaches. Cytotoxic level of SPT on cell survival were detected using MTS assay. The apoptotic cell death and cell cycle arrest was determined using Annexin V/PI and cell cycle assay, respectively. Transcriptome analysis was performed using RNA-seq, followed by functional and KEGG pathway enrichment analysis. qPCR was used to validate the different genes. SPT treated HepG2 and Hep3B cells induced cytotoxicity having IC50 values of 1.13 mM and 0.91 mM, respectively. SPT caused mitotic arrest in G0/G1 phase at 48 h and subsequent apoptotic cell death. RNA-seq revealed a total number of 822 and 1075 differentially expressed genes (DEGs) which after SPT treatment in HepG2 and Hep3B cells, respectively. Functional and KEGG pathway enrichment results suggested that there are several genes involved to induce apoptosis related pathways. The DEGs in p53 signaling pathway may have closely relationships to the cells apoptosis caused by SPT treatment. qPCR results validated dynamic changes in p53 signaling pathway, DNA replication and cell cycle related genes, such as CDKN1A, SERPINE1, PMAIP1, MCM3, MCM5 and MCM6. In vitro experiments and RNA-seq analysis show anti-proliferative and apoptotic effect of SPT in HCC cells. Further studies might help in understanding the molecular mechanisms of SPT. •SPT inhibited proliferation of HCC cells in dose and time dependent manner.•SPT induced apoptotic cell death and stimulated cell cycle arrest at G0/G1 phase in HCC cells.•The transcriptome analysis of SPT in HCC is revealed for the first time.•SPT treated HCC cells revealed more than 800 differentially expressed genes using RNA-seq analysis.•p53 signaling pathway, DNA replication and cell cycle related genes showed dynamic changes.