Cytoplasmic vacuolization in cell death and survival

Shubin, Andrey V.; Demidyuk, Ilya V.; Komissarov, Alexey A.; Rafieva, Lola M.; Kostrov, Sergey V.

doi:10.18632/oncotarget.10150

Cited by 301 publications

(262 citation statements)

References 303 publications

(353 reference statements)

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“…18,21,33 We observed that δ-TT induces morphological changes, with an intense cytoplasmic vacuolation in both CRPC cells. 18,21,33 We observed that δ-TT induces morphological changes, with an intense cytoplasmic vacuolation in both CRPC cells.…”

Section: Discussionmentioning

confidence: 64%

“…52,53 TTs (specifically γ-and δ-TT) were shown to induce apoptosis by triggering the ER stress branches in cervical cancer, 30 breast cancer 54 and melanoma cells. 18,20,33 This makes these types of cell death a promising target for novel therapeutic strategies. 55,56 Here, we also observed that abrogation of apoptosis by the pancaspase inhibitor Z-VAD-FMK significantly, but not completely, reverted the cytotoxic effect of δ-TT on CRPC cells.…”

Section: Discussionmentioning

confidence: 99%

“…29 In line with these observations, both the ER stress and the autophagy pathways were reported to mediate the anti-cancer activity of several natural compounds. 33 Among them, paraptosis is characterized by: Thus, an additional programmed cell death modality might be involved in the activity of the tocotrienol.…”

Section: Discussionmentioning

confidence: 99%

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δ‐Tocotrienol induces apoptosis, involving endoplasmic reticulum stress and autophagy, and paraptosis in prostate cancer cells

et al. 2019

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Objectives: Prostate cancer, after the phase of androgen dependence, may progress to the castration-resistant prostate cancer (CRPC) stage, with resistance to standard therapies. Vitamin E-derived tocotrienols (TTs) possess a significant antitumour activity. Here, we evaluated the anti-cancer properties of δ-TT in CRPC cells (PC3 and DU145) and the related mechanisms of action. Materials and methods:MTT, Trypan blue and colony formation assays were used to assess cell viability/cell death/cytotoxicity. Western blot, immunofluorescence and MTT analyses were utilized to investigate apoptosis, ER stress and autophagy.Morphological changes were investigated by light and transmission electron microscopy. Results:We demonstrated that δ-TT exerts a cytotoxic/proapoptotic activity in CRPC cells. We found that in PC3 cells: (a) δ-TT triggers both the endoplasmic reticulum (ER) stress and autophagy pathways; (b) autophagy induction is related to the ER stress, and this ER stress/autophagy axis is involved in the antitumour activity of δ-TT; in autophagy-defective DU145 cells, only the ER stress pathway is involved in the proapoptotic effects of δ-TT; (c) in both CRPC cell lines, δ-TT also induces an intense vacuolation prevented by the ER stress inhibitor salubrinal and the protein synthesis inhibitor cycloheximide, together with increased levels of phosphorylated JNK and p38, supporting the induction of paraptosis by δ-TT.Conclusions: These data demonstrate that apoptosis, involving ER stress and autophagy (in autophagy positive PC3 cells), and paraptosis are involved in the anti-cancer activity of δ-TT in CRPC cells.

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Section: Discussionmentioning

confidence: 64%

Section: Discussionmentioning

confidence: 99%

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δ‐Tocotrienol induces apoptosis, involving endoplasmic reticulum stress and autophagy, and paraptosis in prostate cancer cells

et al. 2019

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“…3c). Vacuole formation in mammalian cells is a well-known morphological phenomenon when cells are exposed to kinds of pathogens and compounds, and always accompanies cell death [14]. …”

Section: Resultsmentioning

confidence: 99%

Magmas inhibition as a potential treatment strategy in malignant glioma

Lomeli

Bota

et al. 2018

J Neurooncol

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Purpose Magmas (mitochondria-associated protein involved in granulocyte-macrophage colony-stimulating factor signal transduction) is a nuclear gene that encodes the mitochondrial import inner membrane translocase subunit Tim16. Magmas is highly conserved, ubiquitously expressed in mammalian cells, and is essential for cell viability. Magmas expression levels are increased in prostate cancers and pituitary adenomas. Moreover, silencing Magmas by RNAi sensitizes pituitary adenoma cells to pro-apoptotic stimuli and induces a G0/G1 accumulation. The aim of this study was to examine whether inhibition of Magmas by small molecule inhibitors could be beneficial for the treatment of malignant gliomas. Methods We evaluated the expression of Magmas in patient-derived glioblastoma tissue samples and xenograft models. We studied the feasibility of a small molecule Magmas inhibitor (BT#9) as a therapeutic agent in stable human glioma cell lines and high-grade patient derived glioma stem-like cells. Results Magmas was overexpressed in tissue sections from glioma patients and xenografts. In vivo studies revealed that BT#9 could cross the blood-brain barrier in the animal model. Magmas inhibition by BT#9 in glioma cell lines significantly decreased cell proliferation, induced apoptosis along with vacuole formation, and blocked migration and invasion. In addition, BT#9 treatment decreased the respiratory function of glioma cells, supporting the role that Magmas serves as a ROS (reactive oxygen species) regulator. Conclusions This is the first study on the role of Magmas in glioma. Our findings suggest that Magmas plays a key role in glioma cell survival and targeting Magmas by small molecule inhibitors may be a therapeutic strategy in gliomas.

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“…Cell death is classified into several types, such as apoptosis, necrosis (necroptosis), autophagy‐associated death, mitotic catastrophe, paraptosis and oncosis . Paraptosis has been characterized by cytoplasmic vacuolization that associates with extensive swelling of endoplasmic reticulum (ER), and mitochondria in some cases, in the absence of typical apoptotic features such as formation of apoptotic bodies and nuclear fragmentation . Several reports have shown that paraptosis or paraptosis‐like cell death (PLCD) is induced by overexpression of oncogenic genes, mutation or deletion of genes related to ER function, and exposure to natural or synthetic compounds .…”

mentioning

confidence: 99%

SNIPER(TACC3) induces cytoplasmic vacuolization and sensitizes cancer cells to Bortezomib

et al. 2017

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We previously developed a hybrid small molecule SNIPER (Specific and Nongenetic IAP‐dependent Protein ERaser) against transforming acidic coiled‐coil‐3 (TACC3), SNIPER(TACC3), that induces proteasomal degradation of TACC3 protein. In this study, we found that SNIPER(TACC3) induces cytoplasmic vacuolization derived from endoplasmic reticulum (ER) and paraptosis‐like cell death selectively in cancer cells. Mechanistic analysis suggests that accumulation of ubiquitylated protein aggregates that requires X‐linked inhibitor of apoptosis protein (XIAP) induces ER stress, which results in ER‐stress responses involving X‐box binding protein‐1 (XBP‐1) and ER‐derived vacuolization in cancer cells. Importantly, inhibition of proteasome enhanced the SNIPER(TACC3)‐induced vacuolization, and the combination treatment of SNIPER(TACC3) and bortezomib exhibited a synergistic anticancer activity in several cancer cell lines. The induction of paraptosis‐like cell death in cancer cells by SNIPER(TACC3) could be applied to treat cancer cells resistant to undergo apoptosis by overexpression of XIAP.

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Cytoplasmic vacuolization in cell death and survival

Cited by 301 publications

References 303 publications

δ‐Tocotrienol induces apoptosis, involving endoplasmic reticulum stress and autophagy, and paraptosis in prostate cancer cells

δ‐Tocotrienol induces apoptosis, involving endoplasmic reticulum stress and autophagy, and paraptosis in prostate cancer cells

Magmas inhibition as a potential treatment strategy in malignant glioma

SNIPER(TACC3) induces cytoplasmic vacuolization and sensitizes cancer cells to Bortezomib

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