Exploring the mechanism of an active ingredient of ginger, dihydrocapsaicin, on triple negative breast cancer based on network pharmacology and <em>in vitro</em> experiments

Luo,Liming; Chen,Yuran; Ma,Qiuting; Huang,Yun; Hong,Tao; Shu,Kun; Liu,Zhiyong

doi:10.3892/ol.2023.13781

Exploring the mechanism of an active ingredient of ginger, dihydrocapsaicin, on triple negative breast cancer based on network pharmacology and in vitro experiments

Authors:
- Liming Luo
- Yuran Chen
- Qiuting Ma
- Yun Huang
- Tao Hong
- Kun Shu
- Zhiyong Liu
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Affiliations: Laboratory Animal Science Center, Jiangxi University of Traditional Chinese Medicine, Nanchang, Jiangxi 330004, P.R. China
Published online on: April 3, 2023 https://doi.org/10.3892/ol.2023.13781
Article Number: 195
Copyright: © Luo et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

To investigate the potential mechanism of ginger in the treatment of triple‑negative breast cancer (TNBC) based on network pharmacology, molecular docking and in vitro cell experiments. The Traditional Chinese Medicine Systems Pharmacology Database And Analysis Platform, the Bioinformatics Analysis Tool For Molecular Mechanism Of Traditional Chinese Medicine and the HERB database and literature search were used to search for the main active compounds of ginger. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were used to predict the possible molecular mechanism and signaling pathway of ginger in the treatment of triple negative breast cancer. The key core genes of ginger in the treatment of triple negative breast cancer were docked with the active ingredients of ginger on the Autodock platform, and the mechanism of ginger on triple negative breast cancer was further verified by in vitro cell experiments. As a result, 10 effective components, 27 potential targets and 10 Protein‑Protein Interaction core genes were predicted in the treatment of triple negative breast cancer with ginger, involving 287 biological processes, 18 cellular components and 38 molecular functions. Ginger regulated the proliferation, migration and apoptosis of triple negative breast cancer cells by regulating TNF, IL‑17, FoxO, MAPK, PI3K/AKT and other signaling pathways. The results of molecular docking showed that the lowest binding potential energy between dihydrocapsaicin (DHC) and EGFR protein was ‑7.70 kcal·mol‑1, followed by that between 6‑gingerol and EGFR protein was ‑7.30 kcal·mol‑1 and that between DHC and CASP3 protein was ‑7.20 kcal·mol‑1. In vitro cell experiments showed that ginger could inhibit the proliferation and migration of TNBC MDA‑MB‑231 cells, increase the mRNA expression of Caspase family CASP9 and the protein expression of CASP3 and BAX. Overall, based on the combination of network pharmacology and in vitro cell experiments, ginger has the characteristics of multi‑target in the treatment of TNBC, which may play a regulatory role through the PI3K/AKT family. It provides a reference for the drug development of ginger and the clinical treatment of triple negative breast cancer.

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