Non-apoptotic cell death in malignant tumor cells and natural compounds

Ye, Jing; Zhang, Ruonan; Wu, Fan; Zhai, Li; Wang, Kaifeng; Xiao, Mang; Xie, Tian; Sui, Xinbing

doi:10.1016/j.canlet.2018.01.061

Cited by 86 publications

(56 citation statements)

References 153 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…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%

See 1 more Smart Citation

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

et al. 2019

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionmentioning

confidence: 99%

“…Paraptosis, necroptosis, mitotic catastrophe, anoikis were reported to be typical of apoptosis-resistant tumour cells and to mediate the cytotoxic effects of anti-cancer compounds. 18,20,33 This makes these types of cell death a promising target for novel therapeutic strategies. 33 Among them, paraptosis is characterized by:…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2019

View full text Add to dashboard Cite

show abstract

“…But most cancer cells show resistance to the anticancer therapy and are defective in apoptotic induction ( 160 ). Thus, to deal with this debilitating condition, the researchers have focused their attention on natural products such as Matrine, Saponins, Glabridin, and Platycodin D, which exhibit non-apoptotic programmed cell death ( 160 ). In addition, ribosome-inactivating proteins (RIPs) were exploited as potent cytotoxins that have potential anticancer properties.…”

Section: Targeted Approaches Toward Cancermentioning

confidence: 99%

Immunological Approaches Towards Cancer and Inflammation: A Cross Talk

2018

View full text Add to dashboard Cite

The inflammation is the protective response of the body against various harmful stimuli; however, the aberrant and inappropriate activation tends to become harmful. The acute inflammatory response tends to resolved once the offending agent is subside but this acute response becomes chronic in nature when the body is unable to successfully neutralized the noxious stimuli. This chronic inflammatory microenvironment is associated with the release of various pro-inflammatory and oncogenic mediators such as nitric oxide (NO), cytokines [IL-1β, IL-2, interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α)], growth factor, and chemokines. These mediators make the inflammatory microenvironment more vulnerable toward tumorigenesis. The pro-inflammatory mediators released during the chronic inflammation tends to induce several molecular signaling cascades such as nuclear factor kappa B, MAPKinase, nuclear factor erythroid 2-related factor 2, phosphoinositide-3-kinase, Janus kinases/STAT, Wnt/B-catenin, and cyclic AMP response element binding protein. The immune system and its components have a pleiotropic effect on inflammation and cancer progression. Immune components such as T cells, natural killer cells, macrophages, and neutrophils either inhibit or enhance tumor initiation depending on the type of tumor and immune cells involved. Tumor-associated macrophages and tumor-associated neutrophils are pro-tumorigenic cells highly prevalent in inflammation-mediated tumors. Similarly, presence of T regulatory (Treg) cells in an inflammatory and tumor setting suppresses the immune system, thus paving the way for oncogenesis. However, Treg cells also inhibit autoimmune inflammation. By contrast, cytotoxic T cells and T helper cells confer antitumor immunity and are associated with better prognosis in patients with cancer. Cytotoxic T cells inflict a direct cytotoxic effect on cells expressing oncogenic markers. Currently, several anti-inflammatory and antitumor therapies are under trials in which these immune cells are exploited. Adoptive cell transfer composed of tumor-infiltrating lymphocytes has been tried for the treatment of tumors after their ex vivo expansion. Mediators released by cells in a tumorigenic and inflammatory microenvironment cross talk with nearby cells, either promoting or inhibiting inflammation and cancer. Recently, several cytokine-based therapies are either being developed or are under trial to treat such types of manifestations. Monoclonal antibodies directed against TNF-α, VEGF, and IL-6 has shown promising results to ameliorate inflammation and cancer, while direct administration of IL-2 has been shown to cause tumor regression.

show abstract

“…Currently, apoptosis tolerance-mediated MDR has been considered the most common and complex drug-resistant mechanism [5,33] . However, in addition to apoptosis, anticancer drugs can also trigger other anticancer mechanisms, such as autophagy, MC, ferroptosis, pyroptosis, necrosis and senescence, to inhibit the proliferation of cancer cells and kill them by avoiding the apoptosis-resistant pathway [11,17,34,35] . In our previous studies, we con rmed that BZML has potent anticancer activity and overcomes MDR by inducing MC in A549/Taxol cells, an MDR cell line [24] .…”

Section: Discussionmentioning

confidence: 99%

Survivin Suppression Strengthens BZML-induced Mitotic Catastrophe to Overcome Multidrug Resistance by Removing Senescent A549/Taxol Cells

Bai¹,

Zhou²,

Ye³

et al. 2020

Preprint

View full text Add to dashboard Cite

Background: Mitotic catastrophe (MC) of cancer cells induced by BZML, a novel colchicine-binding site inhibitor, exerts a significant advantage in overcoming multidrug resistance (MDR) in NSCLC. However, the long cellular death process resulting from MC is not beneficial for anticancer treatment. Here, we study the mechanisms underlying MC occurrence and development to promote the development of anticancer therapies based on drug-induced MC.Methods: Cellular senescence was confirmed by morphological features, SA-β-Gal and C12FDG staining. Cell cycle analysis and Hoechst 33342 staining were used to detect MC. Relevant signal transduction pathways and protein location were detected by qRT-PCR, westren blot and immunofluorescence. The half-life of proteins was evaluated using the protein synthesis inhibitor cycloheximide. Flow cytometry, MTT assay, crystal violet staining, Hoechst 33342 staining and cell division detection were performed to determine the effects of BZML and/or YM155 on cell fate. Results: We found that BZML induced p53-dependent cellular senescence in A549/Taxol cells, but not in A549, H1299 and MDA-MB-231 cells. Interestingly, BZML-induced senescence was a secondary effect of MC. In addition, the destruction of the protein-degradation system induced by BZML contributed not only to an increase in p53 protein but also to the accumulation of survivin in the nucleus of A549/Taxol cells. However, in A549 cells, the overexpression of survivin had no effect on apoptosis resistance against BZML and failed to promote BZML-induced MC. The inhibition of survivin did not prevent MC occurrence. Unexpectedly, targeting survivin with YM155 accelerated the death of the MC cells by eliminating senescent cells and strengthening the efficiency of BZML in overcoming the MDR of A549/Taxol cells.Conclusions: Our data suggest that nuclear accumulation of survivin can delay cellular death during MC by promoting the survival of senescent BZML-treated A549/Taxol cells. Further, depending on the dose sequence, combination therapy with YM155 to inhibit survivin might be a new strategy for potentiating BZML-induced MC to overcome MDR during cancer treatment.

show abstract

Non-apoptotic cell death in malignant tumor cells and natural compounds

Cited by 86 publications

References 153 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

Immunological Approaches Towards Cancer and Inflammation: A Cross Talk

Survivin Suppression Strengthens BZML-induced Mitotic Catastrophe to Overcome Multidrug Resistance by Removing Senescent A549/Taxol Cells

Contact Info

Product

Resources

About