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Journal of Traditional Chinese Medicine >

2024 , Vol. 44 >Issue 1: 70 - 77

DOI: https://doi.org/10.19852/j.cnki.jtcm.20231204.001

Original articles

Caffeic acid 3,4-dihydroxyphenethyl ester prevents colorectal cancer through inhibition of multiple cancer-promoting signal pathways in 1,2-Dimethylhydrazine/dextran sodium sulphate mouse model

  • Tao JIN ,
  • Qian ZHOU ,
  • Jichen SHEN ,
  • Zhizhong ZHANG ,
  • Xiaoyuan LIAN
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  • 1 College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China
    2 Pharmaceutical Informatics Institute, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China
    3 Ocean College, Zhoushan Campus of Zhejiang University, Zhoushan 316021, China
    4 College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China

Received date: 2022-07-22

  Accepted date: 2022-11-17

  Online published: 2023-12-04

Supported by

National Natural Science Foundation of China Project: the Investigation of Anti-tumor Target System of Traditional Chinese Medicine(81274137, to Stimulate Research Targeted the Energy Metabolism Network of Tumor Cells)

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Abstract

OBJECTIVE: To elucidate the potential feature and mechanism of the caffeic acid 3,4-dihydroxyphenethyl ester (CADPE) molecule, which can prevent colorectal cancer (CRC) in the 1,2-Dimethylhydrazine (DMH)/dextran sodium sulphate (DSS)-induced mouse model.

METHODS: Institute of cancer research (ICR) male mice were injected with 20 mg/kg DMH for a week. After that, 2% DSS was administered in the drinking water for another 7 d. The CADPE treatment was given to the DMH/DSS induced male mice at three different periods until their sacrifice. Histopathological examination was used for observing the CRC development at colonic mucosa. Immunohistochemistry (IHC), blood cells smearing and crypt damage scoring methods were used for investigating the anti-inflammation feature of CADPE related to CRC. The reversing targets searching method was applied with artificial intelligence (AI), computer-aided drug designing (CADD) and Ingenuity Pathway Analysis (IPA) techniques for predicting the potential targets and mechanism of CADPE highly related to CRC.

RESULTS: The data indicated that CADPE inhibited CRC tumor development in the colitis-associated DMH/DSS induced mouse model after giving the early treatment. CADPE also impeded the acute inflammation by decreasing the infiltration of neutrophils significantly during the initial stage of CRC development. Finally, our data showed that CADPE prevented CRC by blocking active sites of three pivotal protein targets including epidermal growth factor receptor (EGFR), extracellular signal-regulated kinase (ERK) and mammalian target of rapamycin (mTOR) in two major cancer development pathways.

CONCLUSIONS: CADPE effectively prevented CRC at early stage of tumor germination in the DMH/DSS mouse model highly likely due to its anti-acute inflammation characteristic and the ability of blocking EGFR, ERK and mTOR activities in two highly related CRC developing pathways.

Key words： caffeic acids; colorectal neoplasms; inflammation; chemoprevention; Sarcandra glabra

Cite this article

Tao JIN , Qian ZHOU , Jichen SHEN , Zhizhong ZHANG , Xiaoyuan LIAN . Caffeic acid 3,4-dihydroxyphenethyl ester prevents colorectal cancer through inhibition of multiple cancer-promoting signal pathways in 1,2-Dimethylhydrazine/dextran sodium sulphate mouse model[J]. Journal of Traditional Chinese Medicine, 2024 , 44(1) : 70 -77 . DOI: 10.19852/j.cnki.jtcm.20231204.001

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