SK053 triggers tumor cells apoptosis by oxidative stress-mediated endoplasmic reticulum stress

Muchowicz, Angelika; Firczuk, Małgorzata; Wachowska, Malgorzata; Kujawa, Marek; Jankowska‐Steifer, Ewa; Gabrysiak, Magdalena; Pilch, Zofia; Kłossowski, Szymon; Ostaszewski, Ryszard; Gołąb, Jakub

doi:10.1016/j.bcp.2014.12.019

Cited by 20 publications

(21 citation statements)

References 38 publications

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“…Total RNA was isolated, and real-time PCR was done as previously described in detail [18]. The results were analyzed after amplification with LightCycler 480 Software 1.5 (Mannheim, Germany) and normalized for the content of the RPL32 as a housekeeping gene.…”

Section: Real-time Pcrmentioning

confidence: 99%

Inhibition of IDO leads to IL-6-dependent systemic inflammation in mice when combined with photodynamic therapy

Wachowska

Stachura

Tonecka

et al. 2020

Cancer Immunol Immunother

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It was previously reported that the activation of antitumor immune response by photodynamic therapy (PDT) is crucial for its therapeutic outcome. Excessive PDT-mediated inflammation is accompanied by immunosuppressive mechanisms that protect tissues from destruction. Thus, the final effect of PDT strongly depends on the balance between the activation of an adoptive arm of immune response and a range of activated immunosuppressive mechanisms. Here, with flow cytometry and functional tests, we evaluate the immunosuppressive activity of tumor-associated myeloid cells after PDT. We investigate the antitumor potential of PDT combined with indoleamine 2,3-dioxygenase 1 (IDO) inhibitor in the murine 4T1 and E0771 orthotopic breast cancer models. We found that the expression of IDO, elevated after PDT, affects the polarization of T regulatory cells and influences the innate immune response. Our results indicate that, depending on a therapeutic scheme, overcoming IDO-induced immunosuppressive mechanisms after PDT can be beneficial or can lead to a systemic toxic reaction. The inhibition of IDO, shortly after PDT, activates IL-6-dependent toxic reactions that can be diminished by the use of anti-IL-6 antibodies. Our results emphasize that deeper investigation of the physiological role of IDO, an attractive target for immunotherapies of cancer, is of great importance.

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Section: Real-time Pcrmentioning

confidence: 99%

Inhibition of IDO leads to IL-6-dependent systemic inflammation in mice when combined with photodynamic therapy

Wachowska

Stachura

Tonecka

et al. 2020

Cancer Immunol Immunother

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“…In rats with diethylnitrosamine-induced hepatocarcinogenesis, melatonin treatment significantly increases the expression of activating transcription factor 6 (ATF6), C/EBP homologous protein (CHOP), and binding immunoglobulin protein (BIP), which might further promote the incidence of apoptosis [20]. Apoptosis derived from unresolved ER stress has also been observed, indicating that a sustained ER stress response could contribute to tumour cell death [21]. Resistance to cell death is a distinctive characteristic of cancer.…”

Section: Introductionmentioning

confidence: 99%

Melatonin-Induced Changes in Cytosolic Calcium Might be Responsible for Apoptosis Induction in Tumour Cells

Chovancova

Hudecová

Lencesova

et al. 2017

Cell Physiol Biochem

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Background/Aims: Melatonin is a hormone transferring information about duration of darkness to the organism and is known to modulate several signaling pathways in the cells, e.g. generation of endoplasmic reticulum stress, oxidative status of the cells, etc. Melatonin has been shown to exert antiproliferative and cytotoxic effects on various human cancers. We proposed that this hormone can differently affect tumour cells and healthy cells. Methods: We compared the effect of 24 h melatonin treatment on calcium transport (by fluorescent probes FLUO-3AM and Rhod-5N), ER stress (determined as changes in the expression of CHOP, XBP1 and fluorescently, using Thioflavin T), ROS formation (by CellROX® Green/Orange Reagent) and apoptosis induction (by Annexin-V-FLUOS/propidiumiodide) in two tumour cell lines – ovarian cancer cell line A2780 and stable cell line DLD1 derived from colorectal carcinoma, with non-tumour endothelial cell line EA.hy926. Results: Melatonin increased apoptosis in both tumour cell lines more than twice, while in EA.hy926 cells the apoptosis was increased only by 30%. As determined by silencing with appropriate siRNAs, both, type 1 sodium/calcium exchanger and type 1 IP₃ receptor are involved in the apoptosis induction. Antioxidant properties of melatonin were significantly increased in EA.hy926 cells, while in tumour cell lines this effect was much weaker. Conclusion: Taken together, melatonin has different antioxidative effects on tumour cells compared to non-tumour ones; it also differs in the ability to induce apoptosis through the type 1 sodium/calcium exchanger, and type 1 IP₃ receptor. Different targeting of calcium transport systems in tumour and normal, non-tumour cells is suggested as a key mechanism how melatonin can exert its anticancer effects. Therefore, it might have a potential as a novel therapeutic implication in cancer treatment.

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“…It has been documented for some time that under increased OS, rER in oocytes appears denser, and increased in size, consistent with enlarged cisternae [24]. Cellular stress is also produced through shorter electron transport chain in rER, which is responsible for 25% of OS in cells [62,63]. OS also increases calcium release from rER through the ryanodine receptors and inositol-1, 4, 5 triphosphate (IP3R), with the ions being taken up by the mitochondria to facilitate further OS generation [64].…”

Section: Ii) Rough Endoplasmic Reticulum and Oxidative Stressmentioning

confidence: 96%

“…Affected calcium homeostasis impairs the protein folding machinery, leading to accumulated misfolded or unfolded proteins and sequester BiP inside the lumen of rER, thereby elevating the intracellular levels of OS in rER [65]. Several reports exist in the literature describing the increased BiP levels due to OS [63,65,66]. The rER must therefore be capable of stressadapting responses.…”

Section: Ii) Rough Endoplasmic Reticulum and Oxidative Stressmentioning

confidence: 99%

Tocotrienols and Oxidative Stress in Oocytes and Developing Embryos

Kamsani¹,

Rajikin²

2017

JCHS

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This review summarizes the impact of tocotrienols (TCTs) as antioxidants in minimizing oxidative stress (OS), particularly in embryos exposed to OS causing agents. OS level is increased, for example, by nicotine, a major alkaloid content in cigarette, which is also a source of exogenous reactive oxygen species (ROS). Increased nicotine-induced OS increases cell stress response, which is a common trigger leading to embryonic cell death. Having more profound anti-oxidative stress effects than its counterpart tocopherol, TCTs improve blastocyst implantation, foetal growth, pregnancy outcome and survival of the neonates affected by nicotine. In reversing cell developmental arrest caused by nicotine-induced OS, TCTs enhances PDK-1 expression in the P13K/Akt pathway and permit embryonic development beyond the 4- cell stage with the production of more morulae. At the cytoskeletal level, TCTs increase the number of nicotine-induced apoptotic cells, through caspase 8 activation in the mitochondria. TCTs facilitate rough endoplasmic reticulum (rER) stress-mediated apoptosis and autophagy, resulting from nicotine-induced OS. Reduced vesicular population in TCT supplemented oocytes on the other hand may suggest reduced secretion of apoptotic cell bodies thus probably minimizing vesicular apoptosis during oocyte maturation. Further extensive research is required to develop TCTs as a tool in specific therapeutic approaches to overcome the detrimental effects of OS.

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SK053 triggers tumor cells apoptosis by oxidative stress-mediated endoplasmic reticulum stress

Cited by 20 publications

References 38 publications

Inhibition of IDO leads to IL-6-dependent systemic inflammation in mice when combined with photodynamic therapy

Inhibition of IDO leads to IL-6-dependent systemic inflammation in mice when combined with photodynamic therapy

Melatonin-Induced Changes in Cytosolic Calcium Might be Responsible for Apoptosis Induction in Tumour Cells

Tocotrienols and Oxidative Stress in Oocytes and Developing Embryos

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