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Chalcomoracin promotes apoptosis and endoplasmic reticulum stress in hepatocellular carcinoma cells

The Journal of Antibiotics (2024)Cite this article

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Abstract

Chalcomoracin (CMR), a Diels-Alder adduct obtained from mulberry leaves, demonstrated wide-spectrum anti-cancer activity. Herein, we aimed to explore the function of CMR and how it works in hepatocellular carcinoma (HCC). Human HCC cell lines Hep3B and SNU-387 were cultured and treated with various concentrations of CMR (1.5, 3, and 6 µM). Subsequently, the effects of CMR on cell viability, colony formation, apoptosis, migration, and invasion abilities were studied in vitro. Furthermore, the levels of endoplasmic reticulum (ER) stress-related proteins and mitogen-activated protein kinase (MAPK) pathway-related proteins in cells under CMR exposure were detected using western blot. Experiments in vivo were conducted to examine the effects of CMR on tumor growth in HCC. CMR administration inhibited the viability and clonogenic, migration, and invasion abilities, as well as promoted cell apoptosis and ER stress in Hep3B and SNU-387 cells. In addition, CMR treatment reduced the phosphorylation levels of ERK, P38, and JNK in the MAPK pathway. Moreover, an in vivo study showed that CMR administration could inhibit tumorigenesis and MAPK pathway activity in HCC. Our data indicate that CMR has the potential to inhibit the development of HCC, potentially through the inhibition of the MAPK pathway. These findings suggest that CMR may have promising applications as an anticancer agent in future therapeutics for HCC.

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Data availability

All data generated or analyzed during this study are included in this published article. The datasets used and/or analyzed during the present study are available from the corresponding author on reasonable request.

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Funding

This work was supported by the Science and Technology Program of Fujian Province(Grant No.2020J011159) and Joint Funds for the innovation of science and Technology, Fujian province (Grant No.2021Y9032).

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Authors and Affiliations

  1. Department of Hepatobiliary Pancreatic Surgery, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, Fujian, 350028, China

    Yongliang Cui, Jiahui Lv & Yongping Lai

  2. Department of Intensive Care Unit, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, Fujian, 350028, China

    Liqin Lan

  3. The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, Fujian, 350028, China

    Bixing Zhao

  4. Department of Liver Disease, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, Fujian, 350028, China

    Jinfeng Kong

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  1. Yongliang Cui
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  4. Bixing Zhao
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Contributions

Yongliang Cui and Liqin Lan designed the study, completed the experiment and supervised the data collection, Jiahui Lv analyzed the data, interpreted the data, Bixing Zhao, Jinfeng Kong and Yongping Lai prepare the manuscript for publication and reviewed the draft of the manuscript. All authors have read and approved the manuscript.

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Correspondence to Jinfeng Kong or Yongping Lai.

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The authors declare no competing interests.

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Ethical approval was obtained from the Ethics Committee of Mengchao Hepatobiliary Hospital of Fujian Medical University (Approval No.MCHH-AEC-2023-07).

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Cui, Y., Lan, L., Lv, J. et al. Chalcomoracin promotes apoptosis and endoplasmic reticulum stress in hepatocellular carcinoma cells. J Antibiot (2024). https://doi.org/10.1038/s41429-024-00732-4

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  • DOI: https://doi.org/10.1038/s41429-024-00732-4

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