Anti-tumor target screening of sea cucumber saponin Frondoside A: a bioinformatics and molecular docking analysis

Guangchun Liu; Shenglin Zhang; Ruoyan Lin; Xudong Cao; Lihong Yuan

doi:10.3389/fonc.2023.1307838

Anti-tumor target screening of sea cucumber saponin Frondoside A: a bioinformatics and molecular docking analysis

Front Oncol. 2023 Dec 8:13:1307838. doi: 10.3389/fonc.2023.1307838. eCollection 2023.

Authors

Guangchun Liu¹, Shenglin Zhang¹, Ruoyan Lin¹, Xudong Cao², Lihong Yuan¹

Affiliations

¹ School of Biosciences and Biopharmaceutics, Guangdong Pharmaceutical University, Guangzhou, China.
² Deparment of Chemical and Biological Engineering, University of Ottawa, Ottawa, ON, Canada.

Abstract

Cancer remains the leading cause of death worldwide. In spite of significant advances in targeted and immunotherapeutic approaches, clinical outcomes for cancer remain poor. The aim of the present study was to investigate the potential mechanisms and therapeutic targets of Frondoside A for the treatment of liver, pancreatic, and bladder cancers. The data presented in our study demonstrated that Frondoside A reduced the viability and migration of HepG2, Panc02, and UM-UC-3 cancer cell in vitro. Moreover, we utilized the GEO database to screen and identify for differentially expressed genes (DEGs) in liver, pancreatic, and bladder cancers, which resulted in the identification of 714, 357, and 101 DEGs, respectively. Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway annotation were performed using the Metascape database for DEGs that were significantly associated with cancer development. The protein-protein interaction (PPI) networks of the identified DEGs in liver, pancreatic, and bladder cancers were analyzed using Cytoscape 3.9.0 software, and subsequently identified potential key genes that were associated with these networks. Subsequently, their prognostic values were assessed by gene expression level analysis and Kaplan-Meier survival analysis (GEPIA). Furthermore, we utilized TIMER 2.0 to investigate the correlation between the expression of the identified key gene and cancer immune infiltration. Finally, molecular docking simulations were performed to assess the affinity of Frondoside A and key genes. Our results showed a significant correlation between these DEGs and cancer progression. Combined, these analyses revealed that Frondoside A involves in the regulation of multiple pathways, such as drug metabolism, cell cycle in liver cancer by inhibiting the expression of CDK1, TOP2A, CDC20, and KIF20A, and regulates protein digestion and absorption, receptor interaction in pancreatic cancer by down-regulation of ASPM, TOP2A, DLGAP5, TPX2, KIF23, MELK, LAMA3, and ANLN. While in bladder cancer, Frondoside A regulates muscle contraction, complement and coagulation cascade by increase FLNC expression. In conclusion, the present study offers valuable insights into the molecular mechanism underlying the anticancer effects of Frondoside A, and suggests that Frondoside A can be used as a functional food supplement or further developed as a natural anti-cancer drug.

Keywords: Frondoside A; antitumor; integrated bioinformatical analysis; molecular docking; therapeutic target genes.

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This research was funded by the Innovation Team Project of Guangdong Universities (2022KCXTD017). XC is supported by the grant of Guangdong International High-end Talents Exchange Project (Overseas famous experts, YKHZZ [2021] No. 1480). The funders had no role in the study design, the data collection and analysis, the decision to publish, or the preparation of the manuscript.