2. Academic Validation
  3. Paraptosis: a non-classical paradigm of cell death for cancer therapy

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

  • Acta Pharmacol Sin. 2024 Feb;45(2):223-237. doi: 10.1038/s41401-023-01159-7.
Chun-Cao Xu 1,  Yi-Fan Lin 2,  Mu-Yang Huang 1,  Xiao-Lei Zhang 3,  Pei Wang 4,  Ming-Qing Huang 5,  Jin-Jian Lu 6 7 8 9 10
Affiliations

Affiliations

  • 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 College of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou, 350122, China. 2010075@fjtcm.edu.cn.
  • 6 State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao, China. jinjianlu@um.edu.mo.
  • 7 Department of Pharmaceutical Sciences, Faculty of Health Sciences, University of Macau, Macao, China. jinjianlu@um.edu.mo.
  • 8 MoE Frontiers Science Center for Precision Oncology, University of Macau, Macao, China. jinjianlu@um.edu.mo.
  • 9 Guangdong-Hong Kong-Macau Joint Lab on Chinese Medicine and Immune Disease Research, University of Macau, Macao, China. jinjianlu@um.edu.mo.
  • 10 Zhuhai UM Science & Technology Research Institute, Zhuhai, 519000, China. jinjianlu@um.edu.mo.
PMID: 37715003 DOI: 10.1038/s41401-023-01159-7
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.

Keywords

ER stress; cancer therapy; endoplasmic reticulum; mitochondria; paraptosis.

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