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Paraptosis: a non-classical paradigm of cell death for cancer therapy

Acta Pharmacologica Sinica volume 45, pages 223–237 (2024)Cite this article

Abstract

Due to the sustained proliferative potential of cancer cells, inducing cell death is a potential strategy for cancer therapy. Paraptosis is a mode of cell death characterized by endoplasmic reticulum (ER) and/or mitochondrial swelling and cytoplasmic vacuolization, which is less investigated. Considerable evidence shows that paraptosis can be triggered by various chemical compounds, particularly in cancer cells, thus highlighting the potential application of this non-classical mode of cell death in cancer therapy. Despite these findings, there remain significant gaps in our understanding of the role of paraptosis in cancer. In this review, we summarize the current knowledge on chemical compound-induced paraptosis. The ER and mitochondria are the two major responding organelles in chemical compound-induced paraptosis, which can be triggered by the reduction of protein degradation, disruption of sulfhydryl homeostasis, overload of mitochondrial Ca2+, and increased generation of reactive oxygen species. We also discuss the stumbling blocks to the development of this field and the direction for further research. The rational use of paraptosis might help us develop a new paradigm for cancer therapy.

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Fig. 1: Schematic diagram of the process involved in compound-induced paraptosis.
Fig. 2: Schematic diagram of future perspectives in studying paraptosis.

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Acknowledgements

This work is supported by the National Natural Science Foundation of China (No. 81973516), the Science and Technology Development Fund, Macau SAR (File no. 0053-2021-AGJ), the Joint Foundation of Guangdong and Macau for Science and Technology Innovation (2022A0505020024), the 2020 Guangdong Provincial Science and Technology Innovation Strategy Special Fund (Guangdong-Hong Kong-Macau Joint Lab, File No.: 2020B1212030006), the Internal Research Grant of the State Key Laboratory of Quality Research in Chinese Medicine, University of Macau (File No.: SKL-QRCM-IRG2023-011), and the MoE Frontiers Science Center for Precision Oncology in University of Macau.

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Authors and Affiliations

  1. State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao, China

    Chun-cao Xu, Mu-yang Huang & Jin-jian Lu

  2. College of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou, 350122, China

    Yi-fan Lin & Ming-qing Huang

  3. National-Local Joint Engineering Laboratory of Druggability and New Drug Evaluation, Guangdong Key Laboratory of Chiral Molecule and Drug Discovery, School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou, 510080, China

    Xiao-lei Zhang

  4. Department of Pharmacology, School of Pharmacy, Naval Medical University/Second Military Medical University, Shanghai, 200433, China

    Pei Wang

  5. Department of Pharmaceutical Sciences, Faculty of Health Sciences, University of Macau, Macao, China

    Jin-jian Lu

  6. MoE Frontiers Science Center for Precision Oncology, University of Macau, Macao, China

    Jin-jian Lu

  7. Guangdong-Hong Kong-Macau Joint Lab on Chinese Medicine and Immune Disease Research, University of Macau, Macao, China

    Jin-jian Lu

  8. Zhuhai UM Science & Technology Research Institute, Zhuhai, 519000, China

    Jin-jian Lu

Authors
  1. Chun-cao Xu
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  2. Yi-fan Lin
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  3. Mu-yang Huang
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  4. Xiao-lei Zhang
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  5. Pei Wang
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  6. Ming-qing Huang
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  7. Jin-jian Lu
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Contributions

CCX and YFL wrote and edited the manuscript. MYH, XLZ, PW, MQH, and JJL revised the manuscript. JJL provided direction and guidance throughout the preparation of this manuscript. All authors read and approved the final manuscript.

Corresponding authors

Correspondence to Ming-qing Huang or Jin-jian Lu.

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Xu, Cc., Lin, Yf., Huang, My. et al. Paraptosis: a non-classical paradigm of cell death for cancer therapy. Acta Pharmacol Sin 45, 223–237 (2024). https://doi.org/10.1038/s41401-023-01159-7

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