Paraptosis: a non-classical paradigm of cell death for cancer therapy
Chun-cao Xu1,
Yi-fan Lin2,
Mu-yang Huang1,
Xiao-lei Zhang3,
Pei Wang4,
Ming-qing Huang2,
Jin-jian Lu1,5,6,7,8
1 State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao, China
2 College of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou 350122, China
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
4 Department of Pharmacology, School of Pharmacy, Naval Medical University/Second Military Medical University, Shanghai 200433, China
5 Department of Pharmaceutical Sciences, Faculty of Health Sciences, University of Macau, Macao, China
6 MoE Frontiers Science Center for Precision Oncology, University of Macau, Macao, China
7 Guangdong-Hong Kong-Macau Joint Lab on Chinese Medicine and Immune Disease Research, University of Macau, Macao, China
8 Zhuhai UM Science & Technology Research Institute, Zhuhai 519000, China
Correspondence to: Ming-qing Huang: 2010075@fjtcm.edu.cn, Jin-jian Lu: jinjianlu@um.edu.mo,
DOI: 10.1038/s41401-023-01159-7
Received: 20 June 2023
Accepted: 28 August 2023
Advance online: 15 September 2023
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.
