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monotropein Induced Apoptosis and Suppressed Cell Cycle Progression in Colorectal Cancer Cells

Chinese Journal of Integrative Medicine 2024年第1期30卷 25-33页

作者： GAO Quan LI Lin ZHANG Qi-man SHENG Qin-song ZHANG Ji-liang JIN Li-jun SHANG Rui-yan School of Pharmacy and Department of Medical Oncology the Affiliated Hospital of Hangzhou Normal UniversityHangzhou Normal UniversityHangzhou(311121)China Key Laboratory of Elemene Class Anti-Cancer Chinese Medicines Engineering Laboratory of Development and Application of Traditional Chinese MedicinesCollaborative Innovation Center of Traditional Chinese Medicines of Zhejiang ProvinceHangzhou Normal UniversityHangzhou(311121)China Department of Colorectal Surgery the First Affiliated HospitalSchool of MedicineZhejiang UniversityHangzhouChina Beijing Tong Ren Tang Chinese Medicine Co. Ltd.Beijing(100000)China Department of Traditional Chinese Medicine Hangzhou Shangcheng District People's HospitalHangzhou(310006)China Department of Gynecology Hangzhou Women's HospitalHangzhou(310008)China

Objective: To determine whether monotropein has an anticancer effect and explore its potential mechanisms against colorectal cancer(CRC) through network pharmacology and molecular docking combined with experimental verification. Methods: Network pharmacology and molecular docking were used to predict potential targets of monotropein against CRC. Cell counting kit assay, plate monoclonal assay and microscopic observation were used to investigate the antiproliferative effects of monotropein on CRC cells HCT116, HT29 and LoVo. Flow cytometry and scratch assay were used to analyze apoptosis and cell cycle, as well as cell migration, respectively in HCT116, HT29, and LoVo cells. Western blotting was used to detect the expression of proteins related to apoptosis, cell cycle, and cell migration, and the expression of proteins key to the Akt pathway. Results: The Gene Ontology and Reactome enrichment analyses indicated that the anticancer potential of monotropein against CRC might be involved in multiple cancer-related signaling pathways. Among these pathways, RAC-beta serine/threonine-protein kinase(Akt1, Akt2), cyclin-dependent kinase 6(CDK6), matrix metalloproteinase-9(MMP9), epidermal growth factor receptor(EGFR), cell division control protein 42 homolog(CDC42) were shown as the potential anticancer targets of monotropein against CRC. Molecular docking suggested that monotropein may interact with the 6 targets(Akt1, Akt2, CDK6, MMP9, EGFR, CDC42). Subsequently, cell activity of HCT116, HT29 and LoVo cell lines were significantly suppressed by monotropein(Pmonotropein induced cell apoptosis by inhibiting Bcl-2 and increasing Bax, induced G_1–S cycle arrest in colorectal cancer by decreasing the expressions of CyclinD1, CDK4 and CDK6, inhibited cell migration by suppressing the expressions of CDC42 and MMP9(Pmonotropein exerts its antitumor

关键词： monotropein Chinese medicine anticancer activity colorectal cancer cells network pharmacology

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Mechanism Prediction of monotropein for the Treatment of Colorectal Cancer by Network Pharmacology Analysis

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Digital Chinese Medicine 2020年第1期3卷 1-10页

作者： LI Chong HOU Shao-Zhen ZHOU Hua Faculty of Chinese Medicine and State Key Laboratory of Quality Research in Chinese Medicine Macao University of Science and TechnologyTaipaMacao 999078China School of Pharmaceutical Sciences Guangzhou University of Chinese MedicineGuangzhouGuangdong 510006China Joint Laboratory for Translational Cancer Research of Chinese Medicine of the Ministry of Education of the People’s Republic of China Macao University of Science and TechnologyTaipaMacao 999078China

Objective To discover the pharmacological mechanisms of monotropein in colorectal cancer by network pharmacology *** The main-candidate-target network was constructed by the prediction of targets of monotropein, collection of therapeutic targets of colorectal cancer drugs, and construction of the target network and layers of screening. The data were interpreted by pathway enrichment and target score *** This study:(1) Demonstrated the potential of monotropein to be a multi-target drug against colorectal cancer using a computational approach;(2) Discovered 10 candidate targets of monotropein, among which protein kinase B(AKT1)exhibited the highest relevance and importance to colorectal cancer and proto-oncogene tyrosine-protein kinase Src(SRC),Bruton’s tyrosine kinase(BTK), and heat shock protein HSP 90-alpha(HSP90 AA1) also exhibited high relevance;(3) Observed 32 possible pathways related to the effects of monotropein on colorectal cancer, which might explain the mechanism of its action;and(4) Established a method to assess the importance of targets in the *** This study offered clues for the mechanism of the bioactivities of monotropein against colorectal cancer by network analysis. monotropein has the potential to be a multi-target drug against colorectal cancer, which lays the foundation for its clinical applications and further study.

关键词： Colorectal cancer monotropein Network pharmacology Target Protein kinase B(AKT1)

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