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Network pharmacological analysis and experimental study of cucurbitacin B in oral squamous cell carcinoma

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Abstract

Oral squamous cell carcinoma (OSCC) is a malignant tumor with a high incidence and poor prognosis. Cucurbitacin B (CuB) is a tetracyclic triterpenoid small-molecule compound extracted from plants, such as Cucurbitaceae and Brassicaceae, which has powerful anticancer effects. However, the effect and mechanism of CuB on OSCC remain unclear. Within the framework of the current study, network pharmacology was used to analyze the relationship between CuB and OSCC. The network pharmacology analysis showed that CuB and OSCC share 134 common targets; among them, PIK3R1, SRC, STAT3, AKT1, and MAPK1 are the key targets. The molecular docking analysis showed that CuB binds five target proteins. The results of the enrichment analysis showed that CuB exerted effects on OSCC through various pathways; of these pathways, PI3K-AKT was the most important pathway. The results of the in vitro cell experiments showed that CuB could inhibit the proliferation and migration of SCC25 and CAL27 cells, block the cell cycle in the G2 phase, induce cell apoptosis, and regulate the protein expression of the PI3K-AKT signaling pathway. The results of the in vivo animal experiments showed that CuB could inhibit 4NQO-induced oral cancer in mice. Therefore, network pharmacology, molecular docking, cell experiments, and animal experiments showed that CuB could play a role in OSCC by regulating multiple targets and pathways.

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The original contributions presented in the study are included in the article/Supplementary Material; further inquiries can be directed to the corresponding author.

Abbreviations

4NQO:

4-Nitroquinoline-1-oxide

AKT1:

AKT Serine/threonine kinase 1

CTD:

Comparative toxicogenomics database

CuB:

Cucurbitacin B

DMSO:

Dimethylsulfoxide

ETCM:

The encyclopedia of traditional Chinese medicine

HERB:

High-throughput experiment- and reference-guided database of TCM

MAPK1:

Mitogen-activated protein kinase 1

OSCC:

Oral squamous cell carcinoma

PIK3R1:

Phosphoinositide-3-kinase regulatory subunit 1

SRC:

Proto-oncogene non-receptor tyrosine kinase SRC

STAT3:

Signal transducer and activator of transcription-3

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Acknowledgements

This work was supported by the Fundamental Research Program of Shanxi Province (Grant No. 202103021223235).

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Authors and Affiliations

  1. Shanxi Province Key Laboratory of Oral Diseases Prevention and New Materials, Shanxi Medical University School and Hospital of Stomatology, Taiyuan, 030001, Shanxi, China

    Zhenyuan Yu, Shuang Liang, Lanting Ji, Wenpeng Yan, Ruifang Gao & Fang Zhang

  2. Department of Physiology, School of Medicine, China Medical University, Taichung City, Taiwan

    YaHsin Cheng

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  1. Zhenyuan Yu
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Contributions

ZY contributed to Conceptualization, Methodology, Validation, Investigation, Formal analysis, Writing of the original draft, Visualization, and Writing, reviewing, & editing of the manuscript. SL contributed to Conceptualization, Methodology, Validation, and Investigation. LJ contributed to Conceptualization, Validation, and Methodology. YC contributed to Conceptualization and Writing, reviewing, & editing of the manuscript. WY contributed to Data curation and Writing, reviewing, & editing of the manuscript. RG contributed to Data curation and Writing, reviewing, & editing of the manuscript. FZ contributed to Conceptualization, Supervision, Project administration, and Writing, reviewing, & editing of the manuscript.

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Correspondence to Fang Zhang.

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Yu, Z., Liang, S., Ji, L. et al. Network pharmacological analysis and experimental study of cucurbitacin B in oral squamous cell carcinoma. Mol Divers (2023). https://doi.org/10.1007/s11030-023-10713-8

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