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

GAO Quan; LI Lin; ZHANG Qi-man; SHENG Qin-song; ZHANG Ji-liang; JIN Li-jun; SHANG Rui-yan

doi:10.1007/s11655-023-3710-4

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

Original Article | Updated：2023-12-20

- Monotropein Induced Apoptosis and Suppressed Cell Cycle Progression in Colorectal Cancer Cells
- Monotropein Induced Apoptosis and Suppressed Cell Cycle Progression in Colorectal Cancer Cells
- 中国结合医学杂志（英文版） 2024年30卷第1期页码：25-33
- Affiliations：
  
  1.School of Pharmacy and Department of Medical Oncology, the Affiliated Hospital of Hangzhou Normal University, Hangzhou Normal University, Hangzhou (311121), China
  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
  3.Department of Colorectal Surgery, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
  4.Beijing Tong Ren Tang Chinese Medicine Co., Ltd., Beijing(100000), China
  5.Department of Traditional Chinese Medicine, Hangzhou Shangcheng District People's Hospital, Hangzhou(310006), China
  6.Department of Gynecology, Hangzhou Women's Hospital, Hangzhou (310008), China
- Author bio：
  
  Dr. JIN Li-jun, E-mail: 58646061@qq.com;
  Dr. SHANG Rui-yan, E-mail: ruiyanshanghzfcyy@163.com
- Funds：
- DOI：10.1007/s11655-023-3710-4
  中图分类号：
- 纸质出版日期：2024-01，
  
  网络出版日期：2023-09-26，
  
  录用日期：2023-07-24
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Monotropein Induced Apoptosis and Suppressed Cell Cycle Progression in Colorectal Cancer Cells[J]. 中国结合医学杂志（英文版）, 2024,30(1):25-33.

GAO Quan, LI Lin, ZHANG Qi-man, et al. Monotropein Induced Apoptosis and Suppressed Cell Cycle Progression in Colorectal Cancer Cells[J]. Chinese Journal of Integrative Medicine, 2024,30(1):25-33.
Monotropein Induced Apoptosis and Suppressed Cell Cycle Progression in Colorectal Cancer Cells[J]. 中国结合医学杂志（英文版）, 2024,30(1):25-33. DOI： 10.1007/s11655-023-3710-4.

GAO Quan, LI Lin, ZHANG Qi-man, et al. Monotropein Induced Apoptosis and Suppressed Cell Cycle Progression in Colorectal Cancer Cells[J]. Chinese Journal of Integrative Medicine, 2024,30(1):25-33. DOI： 10.1007/s11655-023-3710-4.

摘要

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 (

0.05). Furthermore

our research revealed that monotropein 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 (

0.05)

and might play an anticancer role through Akt signaling pathway.

Conclusions:

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.

关键词

Keywords

monotropeinChinese medicineanticancer activitycolorectal cancer cellsnetwork pharmacology

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