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

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Chinese Journal of Integrative Medicine Aims and scope Submit manuscript

Abstract

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 (P<0.05). Furthermore, our research revealed that monotropein induced cell apoptosis by inhibiting Bcl-2 and increasing Bax, induced G1–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 (P<0.05), and might play an anticancer role through Akt signaling pathway.

Conclusion

Monotropein exerts its antitumor effects primarily by arresting the cell cycle, causing cell apoptosis, and inhibiting cell migration. This indicates a high potential for developing novel medication for treating CRC.

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Author information

Authors and Affiliations

  1. School of Pharmacy and Department of Medical Oncology, the Affiliated Hospital of Hangzhou Normal University, Hangzhou Normal University, Hangzhou, 311121, China

    Quan Gao, Lin Li & Qi-man Zhang

  2. Key Laboratory of Elemene Class Anti-Cancer Chinese Medicines; Engineering Laboratory of Development and Application of Traditional Chinese Medicines; Collaborative Innovation Center of Traditional Chinese Medicines of Zhejiang Province, Hangzhou Normal University, Hangzhou, 311121, China

    Quan Gao, Lin Li & Qi-man Zhang

  3. Department of Colorectal Surgery, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China

    Qin-song Sheng

  4. Beijing Tong Ren Tang Chinese Medicine Co., Ltd., Beijing, 100000, China

    Ji-liang Zhang

  5. Department of Traditional Chinese Medicine, Hangzhou Shangcheng District People’s Hospital, Hangzhou, China

    Li-jun Jin

  6. Department of Gynecology, Hangzhou Women’s Hospital, Hangzhou, 310008, China

    Rui-yan Shang

Authors
  1. Quan Gao
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  2. Lin Li
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  3. Qi-man Zhang
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  4. Qin-song Sheng
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  5. Ji-liang Zhang
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  6. Li-jun Jin
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  7. Rui-yan Shang
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Contributions

Shang RY provided financial support, guided the overall idea of the article, and reviewed and edited the final manuscript; Sheng QS provided the cells, and reviewed and edited the final manuscript; Jin LJ initiated the study, developed the concept of the paper, and reviewed and edited the final manuscript; Li L completed the network pharmacology section; Gao Q completed the molecular docking and experimental part; Gao Q and Li L wrote the original manuscript; Zhang QM and Zhang JL contributed to materials information gathering and data analysis. Gao Q and Li L contribute equally to this work as co-first authors.

Corresponding authors

Correspondence to Li-jun Jin or Rui-yan Shang.

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The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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Gao, Q., Li, L., Zhang, Qm. et al. Monotropein Induced Apoptosis and Suppressed Cell Cycle Progression in Colorectal Cancer Cells. Chin. J. Integr. Med. 30, 25–33 (2024). https://doi.org/10.1007/s11655-023-3710-4

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  • DOI: https://doi.org/10.1007/s11655-023-3710-4

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