The emerging role of paraptosis in tumor cell biology: Perspectives for cancer prevention and therapy with natural compounds

Fontana, Fabrizio; Raimondi, Mario; Marzagalli, Monica; Domizio, Alessandro Di; Limonta, Patrizia

doi:10.1016/j.bbcan.2020.188338

Cited by 88 publications

(62 citation statements)

References 109 publications

(114 reference statements)

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“…However, cancer cells have many against apoptosis and differentiation mechanisms to escape death, which were considered to be important reasons for deterioration, drug resistance and recurrence [31,32]. Therefore, it is essential to explore and utilize new methods of cell death for cancer treatment [33,34]. As a natural product, HNK has the advantages of low toxicvity and high efficiency, and is expected to become a potential drug for the treatment of cancer [11,12].…”

Section: Discussionmentioning

confidence: 99%

Honokiol induces paraptosis-like cell death of acute promyelocytic leukemia via mTOR & MAPK signaling pathways activation

et al. 2021

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Acute promyelocytic leukemia (APL) is a blood system disease caused by the accumulation of a large number of immature blood cells in bone marrow. Although the introduction of all-trans retinoic acid (ATRA) and arsenic has reached a high level of complete remission rate and 5-year disease-free survival rate, the occurrence of various adverse reactions still severely affects the quality of life of patients. As a natural product, honokiol (HNK) has the advantages of low toxicity and high efficiency, and it is a potential drug for the treatment of cancer. Since cancer cells can escape apoptotic cell death through multiple adaptive mechanisms, HNK, a drug that induces cancer cell death in a nonapoptotic way, has attracted much interest. We found that HNK reduced the viability of human APL cell line (NB4 cells) by inducing paraptosis-like cell death. The process was accompanied by excessive reactive oxygen species (ROS), mitochondrial damage, endoplasmic reticulum stress, and increased microtubule-associated protein 1 light chain 3 (LC3) processing. The inactivation of proteasome activity was the main cause of misfolded and unfolded protein accumulation in endoplasmic reticulum, such as LC3II/I and p62. This phenomenon could be alleviated by adding cycloheximide (CHX), a protein synthesis inhibitor. We found that mTOR signaling pathway participated in paraptosis-like cell death induced by HNK in an autophagy-independent process. Moreover, the mitogen-activated protein kinase (MAPK) signaling pathway induced paraptosis of NB4 cells by promoting endoplasmic reticulum stress. In summary, these findings indicate that paraptosis may be a new way to treat APL, and provide novel insights into the potential mechanism of paraptosis-like cell death.

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Section: Discussionmentioning

confidence: 99%

Honokiol induces paraptosis-like cell death of acute promyelocytic leukemia via mTOR & MAPK signaling pathways activation

et al. 2021

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“…The term "paraptosis" was first introduced to describe a form of programmed cell death displaying cytoplasmic vacuolation consisting in mitochondrial and/or endoplasmic reticulum (ER) dilation (Sperandio et al, 2000). Paraptosis was initially observed in 293T cells and mouse embryonic fibroblasts overexpressing insulin-like growth factor 1 receptor (IGF-1R) (Sperandio et al, 2000) and was subsequently shown to be induced by different natural compounds in vitro and in vivo in tumor cells (Lee et al, 2016;Fontana et al, 2020b). In addition, paraptosis appears to be implicated in neurodegeneration (Wei et al, 2015).…”

Section: Introductionmentioning

confidence: 99%

Intracellular Ca2 + Imbalance Critically Contributes to Paraptosis

Kim

Lee

Seo

et al. 2021

Front. Cell Dev. Biol.

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Paraptosis is a type of programmed cell death that is characterized by dilation of the endoplasmic reticulum (ER) and/or mitochondria. Since paraptosis is morphologically and biochemically different from apoptosis, understanding its regulatory mechanisms may provide a novel therapeutic strategy in malignant cancer cells that have proven resistant to conventional pro-apoptotic treatments. Relatively little is known about the molecular basis of paraptosis, but perturbations of cellular proteostasis and ion homeostasis appear to critically contribute to the process. Ca2+ transport has been shown to be important in the paraptosis induced by several natural products, metal complexes, and co-treatment with proteasome inhibitors and certain Ca2+-modulating agents. In particular, the Ca2+-mediated communication between the ER and mitochondria plays a crucial role in paraptosis. Mitochondrial Ca2+ overload from the intracellular Ca2+-flux system located at the ER–mitochondrial axis can induce mitochondrial dilation during paraptosis, while the accumulation of misfolded proteins within the ER lumen is believed to exert an osmotic force and draw water from the cytoplasm to distend the ER lumen. In this process, Ca2+ release from the ER also critically contributes to aggravating ER stress and ER dilation. This review focuses on the role of Ca2+ transport in paraptosis by summarizing the recent findings related to the actions of Ca2+-modulating paraptosis-inducing agents and discussing the potential cancer therapeutic strategies that may effectively induce paraptosis via Ca2+ signaling.

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“…Various research studies have reported that apoptosis induction is a cellular pathway for removing tumor cells [20,21]. Another mechanism is the immunity reinforcement by which tumor cells are killed through specific-tumor B and T cells [22].…”

Section: Discussionmentioning

confidence: 99%

Secreted Chemicals From Probiotic Bacteria Potentiate Th1 Pattern of Immune Cells and Apoptosis Induction in Breast Cancer and Gastric Adenocarcinoma Cell Lines

2020

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Cancer is one of the main causes of mortality. Therapeutic importance in some diseases, especially cancers has led to considering the anti-cancer effects of probiotics more than ever. Probiotics have stimulatory effects on the immunity and suppressor effects on cancer activity. Various studies report that probiotic bacteria have cytotoxicity effects on different types of solid tumors. In this research, we evaluated the synergic effect of secretory chemicals of Lactobacillus and Bifidobacterium bacteria on cytotoxic potency of breast and gastrointestinal cancer cell lines. Bifidobacterium bifidum and Lactobacillus acidophilus were cultured in MRS broth. Cytotoxicity assay was performed on AGS, MCF-7 cell lines, and peripheral mononuclear cells after treatment with bacteria extractions by MTT test. β-actin, Bcl2, Bax, TNF-α, and IFN-γ gene expression levels were evaluated in treated cell lines by real-time PCR method. The result of cytotoxicity assay showed that the obtained extraction from the bacterial cultures has a higher killing effect on cancer cells compared with normal cells. Results of gene expression indicated a significant increase in Bax and Bcl2 gene expression in cancer cells. TNF-α gene expression increased significantly as compared with the control group. The obtained extraction from probiotics culture can induce death in cancer cells through the apoptosis mechanism and improve the cellular immune response, i.e., T helper 1 cytokine profile.

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The emerging role of paraptosis in tumor cell biology: Perspectives for cancer prevention and therapy with natural compounds

Cited by 88 publications

References 109 publications

Honokiol induces paraptosis-like cell death of acute promyelocytic leukemia via mTOR & MAPK signaling pathways activation

Honokiol induces paraptosis-like cell death of acute promyelocytic leukemia via mTOR & MAPK signaling pathways activation

Intracellular Ca2 + Imbalance Critically Contributes to Paraptosis

Secreted Chemicals From Probiotic Bacteria Potentiate Th1 Pattern of Immune Cells and Apoptosis Induction in Breast Cancer and Gastric Adenocarcinoma Cell Lines

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