Paraptosis: a Non-classical Paradigm of Cell Death for Cancer Therapy

Overview

Journal Acta Pharmacol Sin

Specialty Pharmacology

Date 2023 Sep 15

PMID 37715003

Authors

Chun-Cao Xu

Yi-Fan Lin

Mu-Yang Huang

Xiao-Lei Zhang

Pei Wang

Ming-Qing Huang

Jin-Jian Lu

Affiliations

Soon will be listed here.

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 Ca, 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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References

Fontana F, Raimondi M, Marzagalli M, Di Domizio A, Limonta P . The emerging role of paraptosis in tumor cell biology: Perspectives for cancer prevention and therapy with natural compounds. Biochim Biophys Acta Rev Cancer. 2020; 1873(2):188338. DOI: 10.1016/j.bbcan.2020.188338. View

Wang Y, Li X, Wang L, Ding P, Zhang Y, Han W . An alternative form of paraptosis-like cell death, triggered by TAJ/TROY and enhanced by PDCD5 overexpression. J Cell Sci. 2004; 117(Pt 8):1525-32. DOI: 10.1242/jcs.00994. View

Liu X, Gu Y, Bian Y, Cai D, Li Y, Zhao Y . Honokiol induces paraptosis-like cell death of acute promyelocytic leukemia via mTOR & MAPK signaling pathways activation. Apoptosis. 2021; 26(3-4):195-208. PMC: 8016806. DOI: 10.1007/s10495-020-01655-9. View

Vandereyken K, Sifrim A, Thienpont B, Voet T . Methods and applications for single-cell and spatial multi-omics. Nat Rev Genet. 2023; 24(8):494-515. PMC: 9979144. DOI: 10.1038/s41576-023-00580-2. View

Rogov V, Dotsch V, Johansen T, Kirkin V . Interactions between autophagy receptors and ubiquitin-like proteins form the molecular basis for selective autophagy. Mol Cell. 2014; 53(2):167-78. DOI: 10.1016/j.molcel.2013.12.014. View

Yoon M, Kim E, Lim J, Kwon T, Choi K . Superoxide anion and proteasomal dysfunction contribute to curcumin-induced paraptosis of malignant breast cancer cells. Free Radic Biol Med. 2009; 48(5):713-26. DOI: 10.1016/j.freeradbiomed.2009.12.016. View

Sperandio S, de Belle I, Bredesen D . An alternative, nonapoptotic form of programmed cell death. Proc Natl Acad Sci U S A. 2000; 97(26):14376-81. PMC: 18926. DOI: 10.1073/pnas.97.26.14376. View

Guo C, Liu P, Deng G, Han Y, Chen Y, Cai C . Honokiol induces ferroptosis in colon cancer cells by regulating GPX4 activity. Am J Cancer Res. 2021; 11(6):3039-3054. PMC: 8263670. View

Chen X, Chen X, Zhang X, Wang L, Cao P, Rajamanickam V . Curcuminoid B63 induces ROS-mediated paraptosis-like cell death by targeting TrxR1 in gastric cells. Redox Biol. 2018; 21:101061. PMC: 6306695. DOI: 10.1016/j.redox.2018.11.019. View

10.

Kim R, Hashimoto A, Markosyan N, Tyurin V, Tyurina Y, Kar G . Ferroptosis of tumour neutrophils causes immune suppression in cancer. Nature. 2022; 612(7939):338-346. PMC: 9875862. DOI: 10.1038/s41586-022-05443-0. View

11.

Zheng H, Dong Y, Li L, Sun B, Liu L, Yuan H . Novel Benzo[a]quinolizidine Analogs Induce Cancer Cell Death through Paraptosis and Apoptosis. J Med Chem. 2016; 59(10):5063-76. DOI: 10.1021/acs.jmedchem.6b00484. View

12.

Gorrini C, Harris I, Mak T . Modulation of oxidative stress as an anticancer strategy. Nat Rev Drug Discov. 2013; 12(12):931-47. DOI: 10.1038/nrd4002. View

13.

Gandin V, Pellei M, Tisato F, Porchia M, Santini C, Marzano C . A novel copper complex induces paraptosis in colon cancer cells via the activation of ER stress signalling. J Cell Mol Med. 2011; 16(1):142-51. PMC: 3823100. DOI: 10.1111/j.1582-4934.2011.01292.x. View

14.

Hanahan D, Weinberg R . Hallmarks of cancer: the next generation. Cell. 2011; 144(5):646-74. DOI: 10.1016/j.cell.2011.02.013. View

15.

Zheng H, Liu Q, Wang S, Liu X, Ma M, Shen T . Epimedokoreanin B inhibits the growth of lung cancer cells through endoplasmic reticulum stress-mediated paraptosis accompanied by autophagosome accumulation. Chem Biol Interact. 2022; 366:110125. DOI: 10.1016/j.cbi.2022.110125. View

16.

Nedungadi D, Binoy A, Pandurangan N, Pal S, Nair B, Mishra N . 6-Shogaol induces caspase-independent paraptosis in cancer cells via proteasomal inhibition. Exp Cell Res. 2018; 364(2):243-251. DOI: 10.1016/j.yexcr.2018.02.018. View

17.

Hager S, Korbula K, Bielec B, Grusch M, Pirker C, Schosserer M . The thiosemicarbazone MeNNMe induces paraptosis by disrupting the ER thiol redox homeostasis based on protein disulfide isomerase inhibition. Cell Death Dis. 2018; 9(11):1052. PMC: 6189190. DOI: 10.1038/s41419-018-1102-z. View

18.

Pang H, Li X, Zhao Y, Kang J, Li J, Tian W . Confirming whether novel rhein derivative 4a induces paraptosis-like cell death by endoplasmic reticulum stress in ovarian cancer cells. Eur J Pharmacol. 2020; 886:173526. DOI: 10.1016/j.ejphar.2020.173526. View

19.

Lee D, Kim I, Saha S, Choi K . Paraptosis in the anti-cancer arsenal of natural products. Pharmacol Ther. 2016; 162:120-33. DOI: 10.1016/j.pharmthera.2016.01.003. View

20.

Chen M, Mao A, Xu M, Weng Q, Mao J, Ji J . CRISPR-Cas9 for cancer therapy: Opportunities and challenges. Cancer Lett. 2019; 447:48-55. DOI: 10.1016/j.canlet.2019.01.017. View