Transcriptome Analysis Reveals the Anti-cancerous Mechanism of Licochalcone A on Human Hepatoma Cell HepG2

Abstract

Hepatocellular carcinoma is a malignancy with a low survival rate globally, and there is imperative to unearth novel natural phytochemicals as effective therapeutic strategies. Licochalcone A is a chalcone from Glycyrrhiza that displayed various pharmacological efficacy. A globally transcriptome analysis was carried out to reveal the gene expression profiling to explore Licochalcone A's function as an anti-cancer phytochemical on HepG2 cells and investigate its potential mechanisms. Altogether, 6,061 dysregulated genes were detected (3,414 up-regulated and 2,647 down-regulated). SP1 was expected as the transcription factor that regulates the functions of most screened genes. GO and KEGG analysis was conducted, and the MAPK signaling pathway and the FoxO signaling pathway were two critical signal pathways. Protein-protein interaction (PPI) network analysis based on STRING platform to discover the hub genes (MAPK1, ATF4, BDNF, CASP3, etc.) in the MAPK signaling pathway and (AKT3, GADD45A, IL6, CDK2, CDKN1A, etc.) the FoxO signaling pathway. The protein level of essential genes that participated in significant pathways was consistent with the transcriptome data. This study will provide an inclusive understanding of the potential anti-cancer mechanism of Licochalcone A on hepatocellular, signifying Licochalcone A as a promising candidate for cancer therapy.

Anticancer effects of licochalcones: A review of the mechanisms

“…Through these effects, LA (30–70 μM) finally induces apoptosis in HepG2 cells ( Niu et al, 2018 ; Wang et al, 2018 ). LA (70 μM) can induce apoptosis of HepG2 cells by regulating the MAPK and FoxO signaling pathways ( Wang et al, 2021 ). Likewise, LB (10–120 μM) induces apoptosis in HepG2 cells by activating the extrinsic apoptotic pathway (i.e., increasing the expression of TNFR1, Fas, Fas-L, caspase-8, JUN, and Fos) and mitochondrial apoptosis pathway (i.e., increasing the expression of Bak, caspase-9, and caspase-3) ( Wang et al, 2019 ).…”

Role of Licochalcone A in Potential Pharmacological Therapy: A Review

“…LA also reduced the efflux of doxorubicin and temozolomide from BCRP-mediated BCRP-MDCKII cells by downregulating the expression of breast cancer resistance protein (BCRP) ( Fan et al, 2019 ). Based on DEGs and GO and KEGG enrichment, LA showed antitumor activity against HepG2 cells, in which MAPK and FoxO signaling played essential roles ( Wang et al, 2021 ). In gefitinib-resistant non-small cell lung cancer cells (H1975), LA also reduced Hsp90 activity in gefitinib-resistant NSCLC cells (H1975) via binding to the N -terminal ATP binding site of Hsp90 to reduce drug resistance ( Seo, 2013 ).…”

Identification of an immune-related 6-lncRNA panel with a good performance for prognostic prediction in hepatocellular carcinoma by integrated bioinformatics analysis

“…long non-coding RNA (lncRNA) is just one of them. [5][6][7][8] Multiple studies have shown that the expression of many lncRNAs exhibits widespread interference in HCC and is deeply involved in regulating the occurrence, development, and treatment of HCC. [9][10][11] Mediating epigenetic modification, participating in the competitive endogenous RNA mechanism, and modulating the activity of transcription factors and mRNA stability are important ways for lncRNAs to affect HCC.…”