TY - JOUR
T1 - Paraptosis
T2 - a unique cell death mode for targeting cancer
AU - Hanson, Sweata
AU - Dharan, Aiswarya
AU - Jinsha, P. V.
AU - Pal, Sanjay
AU - Nair, Bipin G.
AU - Kar, Rekha
AU - Mishra, Nandita
N1 - Funding Information:
NM is thankful to DST, India for their research grant (DST: SB/FT/LS144/2012). We acknowledge Amrita Vishwa Vidyapeetham for their support.
Funding Information:
SH is supported by Amrita Vishwa Vidyapeetham JRF fellowship and JPV by University Grants Commission JRF fellowship (NTA Ref. No. 211610019820) India. This work was supported by Institutional funding (Amrita Vishwa Vidyapeetham).
Publisher Copyright:
Copyright © 2023 Hanson, Dharan, P. V., Pal, Nair, Kar and Mishra.
PY - 2023
Y1 - 2023
N2 - Programmed cell death (PCD) is the universal process that maintains cellular homeostasis and regulates all living systems’ development, health and disease. Out of all, apoptosis is one of the major PCDs that was found to play a crucial role in many disease conditions, including cancer. The cancer cells acquire the ability to escape apoptotic cell death, thereby increasing their resistance towards current therapies. This issue has led to the need to search for alternate forms of programmed cell death mechanisms. Paraptosis is an alternative cell death pathway characterized by vacuolation and damage to the endoplasmic reticulum and mitochondria. Many natural compounds and metallic complexes have been reported to induce paraptosis in cancer cell lines. Since the morphological and biochemical features of paraptosis are much different from apoptosis and other alternate PCDs, it is crucial to understand the different modulators governing it. In this review, we have highlighted the factors that trigger paraptosis and the role of specific modulators in mediating this alternative cell death pathway. Recent findings include the role of paraptosis in inducing anti-tumour T-cell immunity and other immunogenic responses against cancer. A significant role played by paraptosis in cancer has also scaled its importance in knowing its mechanism. The study of paraptosis in xenograft mice, zebrafish model, 3D cultures, and novel paraptosis-based prognostic model for low-grade glioma patients have led to the broad aspect and its potential involvement in the field of cancer therapy. The co-occurrence of different modes of cell death with photodynamic therapy and other combinatorial treatments in the tumour microenvironment are also summarized here. Finally, the growth, challenges, and future perspectives of paraptosis research in cancer are discussed in this review. Understanding this unique PCD pathway would help to develop potential therapy and combat chemo-resistance in various cancer.
AB - Programmed cell death (PCD) is the universal process that maintains cellular homeostasis and regulates all living systems’ development, health and disease. Out of all, apoptosis is one of the major PCDs that was found to play a crucial role in many disease conditions, including cancer. The cancer cells acquire the ability to escape apoptotic cell death, thereby increasing their resistance towards current therapies. This issue has led to the need to search for alternate forms of programmed cell death mechanisms. Paraptosis is an alternative cell death pathway characterized by vacuolation and damage to the endoplasmic reticulum and mitochondria. Many natural compounds and metallic complexes have been reported to induce paraptosis in cancer cell lines. Since the morphological and biochemical features of paraptosis are much different from apoptosis and other alternate PCDs, it is crucial to understand the different modulators governing it. In this review, we have highlighted the factors that trigger paraptosis and the role of specific modulators in mediating this alternative cell death pathway. Recent findings include the role of paraptosis in inducing anti-tumour T-cell immunity and other immunogenic responses against cancer. A significant role played by paraptosis in cancer has also scaled its importance in knowing its mechanism. The study of paraptosis in xenograft mice, zebrafish model, 3D cultures, and novel paraptosis-based prognostic model for low-grade glioma patients have led to the broad aspect and its potential involvement in the field of cancer therapy. The co-occurrence of different modes of cell death with photodynamic therapy and other combinatorial treatments in the tumour microenvironment are also summarized here. Finally, the growth, challenges, and future perspectives of paraptosis research in cancer are discussed in this review. Understanding this unique PCD pathway would help to develop potential therapy and combat chemo-resistance in various cancer.
KW - alternative cell death
KW - apoptosis
KW - cancer
KW - cancer therapy
KW - paraptosis
KW - programmed cell death
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U2 - 10.3389/fphar.2023.1159409
DO - 10.3389/fphar.2023.1159409
M3 - Review article
C2 - 37397502
AN - SCOPUS:85164393057
SN - 1663-9812
VL - 14
JO - Frontiers in Pharmacology
JF - Frontiers in Pharmacology
M1 - 1159409
ER -