This study investigated whether kaempferol could inhibit ovarian cancer (OC) by activation of endoplasmic reticulum (ER) stress and autophagy, and tested its effect on the sensitivity of OC cells to cisplatin (cis-diamminedichloroplatinum, DPP). To study the effect of kaempferol on activation of ER stress and autophagy and find out whether its mechanism of action involves calcium (Ca2+), A2780 OC cells were cultured in DMEM/F12 for 24 h with or without kaempferol (40 μmol/l) in the presence or absence of autophagy or ER stress inhibitors or a calcium chelator. To study the effect of kaempferol on the sensitivity of OC cells to DPP and the potential involvement of modulation of protein kinase B (Akt) expression, A2780 OC were incubated with kaempferol and increasing concentrations of DPP (0-20 μmol/l) and then with kaempferol at its predetermined IC50 (6.8 μmol/l). Compared to control cells, kaempferol increased cell apoptosis (158 %) and decreased viability (53.17 %) and proliferation (49.17 %) of A2780 OC cells. Concomitantly, it increased the protein levels of GRP78, PERK, ATF6, IRE-1, LC3II, beclin 1, and caspase 4, thus suggesting activation of cytotoxic autophagy. This was mediated by increasing intracellular Ca+2 levels. In addition, kaempferol increased the sensitivity of A2780 cells to DPP (IC50 from 6.867 ± 0.99 to 3.73 ± 0.59 μmol/l) by decreasing the protein levels of p-Akt (0.31 ± 0.09 vs 0.12 ± 0.005). In conclusion, the findings of this study encourage the use of kaempferol alone or in combination with DPP to inhibit tumorigenesis of ovarian cells.

• MeSH
• apoptóza MeSH
• autofagie * MeSH
• chaperon endoplazmatického retikula BiP MeSH
• cisplatina farmakologie   MeSH
• kempferoly farmakologie   MeSH
• lidé MeSH
• nádorové buněčné linie MeSH
• nádory vaječníků patologie   MeSH
• protoonkogenní proteiny c-akt antagonisté a inhibitory   metabolismus   MeSH
• signální transdukce MeSH
• stres endoplazmatického retikula účinky léků   MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• chaperon endoplazmatického retikula BiP MeSH
• cisplatina MeSH
• HSPA5 protein, human MeSH Prohlížeč
• kempferoly MeSH
• protoonkogenní proteiny c-akt MeSH

The effects of ER stress on protein secretion by cardiac myocytes are not well understood. In this study, the ER stressor thapsigargin (TG), which depletes ER calcium, induced death of cultured neonatal rat ventricular myocytes (NRVMs) in high media volume but fostered protection in low media volume. In contrast, another ER stressor, tunicamycin (TM), a protein glycosylation inhibitor, induced NRVM death in all media volumes, suggesting that protective proteins were secreted in response to TG but not TM. Proteomic analyses of TG- and TM-conditioned media showed that the secretion of most proteins was inhibited by TG and TM; however, secretion of several ER-resident proteins, including GRP78 was increased by TG but not TM. Simulated ischemia, which decreases ER/SR calcium also increased secretion of these proteins. Mechanistically, secreted GRP78 was shown to enhance survival of NRVMs by collaborating with a cell-surface protein, CRIPTO, to activate protective AKT signaling and to inhibit death-promoting SMAD2 signaling. Thus, proteins secreted during ER stress mediated by ER calcium depletion can enhance cardiac myocyte viability.

• Klíčová slova
• Cardiac myocyte death, Cardiokine, Cardioprotection, ER stress, Heart failure, Proteostasis,
• MeSH
• apoptóza MeSH
• autokrinní signalizace MeSH
• biologické markery MeSH
• chaperon endoplazmatického retikula BiP MeSH
• epidermální růstový faktor metabolismus   MeSH
• kardiomyocyty účinky léků   metabolismus   MeSH
• krysa rodu Rattus MeSH
• kultivované buňky MeSH
• membránové glykoproteiny metabolismus   MeSH
• myši MeSH
• náchylnost k nemoci MeSH
• nádorové proteiny metabolismus   MeSH
• parakrinní signalizace MeSH
• proteom * MeSH
• proteomika * metody   MeSH
• sarkoplazmatické retikulum metabolismus   MeSH
• signální transdukce účinky léků   MeSH
• stres endoplazmatického retikula * účinky léků   MeSH
• thapsigargin farmakologie   MeSH
• vápník metabolismus   MeSH
• vápníková signalizace účinky léků   MeSH
• viabilita buněk MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH
• Názvy látek
• biologické markery MeSH
• chaperon endoplazmatického retikula BiP MeSH
• epidermální růstový faktor MeSH
• Hspa5 protein, mouse MeSH Prohlížeč
• membránové glykoproteiny MeSH
• nádorové proteiny MeSH
• proteom * MeSH
• Tdgf1 protein, mouse MeSH Prohlížeč
• thapsigargin MeSH
• vápník MeSH

Cisplatin is a widely used chemotherapeutic agent that is clinically approved to fight both carcinomas and sarcomas. It has relatively high efficiency in treating ovarian cancers and metastatic testicular cancers. It is generally accepted that the major mechanism of cisplatin anti-cancer action is DNA damage. However, cisplatin is also effective in metastatic cancers and should, therefore, affect slow-cycling cancer stem cells in some way. In this review, we focused on the alternative effects of cisplatin that can support a good therapeutic response. First, attention was paid to the effects of cisplatin at the cellular level such as changes in intracellular pH and cellular mechanical properties. Alternative cellular targets of cisplatin, and the effects of cisplatin on cancer cell metabolism and ER stress were also discussed. Furthermore, the impacts of cisplatin on the tumor microenvironment and in the whole organism context were reviewed. In this review, we try to reveal possible causes of the unexpected effectiveness of this anti-cancer drug.

• MeSH
• antitumorózní látky farmakologie   terapeutické užití   MeSH
• biomechanika účinky léků   MeSH
• cisplatina farmakologie   terapeutické užití   MeSH
• koncentrace vodíkových iontů účinky léků   MeSH
• lidé MeSH
• metabolické sítě a dráhy účinky léků   MeSH
• nádorové mikroprostředí účinky léků   MeSH
• nádory farmakoterapie   metabolismus   patologie   MeSH
• stres endoplazmatického retikula účinky léků   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• antitumorózní látky MeSH
• cisplatina MeSH

Ovarian surface epithelium (OSE) forms a single layer of mostly cuboidal cells on surface of mammalian ovaries that is inherently exposed to cell stress evoked by tissue damage every ovulation and declines morphologically after menopause. Endoplasmic reticulum (ER) is a principal cell organelle involved in proteosynthesis, but also integrating various stress signals. ER stress evokes a conserved signaling pathway, the unfolded protein response (UPR), leading to cell death or adaptation to stress conditions. In this work, we document that mouse OSE suffers from ER stress during replicative senescence in vitro, develops abnormalities in ER and initiates UPR. Attenuation of ER stress in senescent OSE by tauroursodeoxycholic acid (TUDCA) reconditions ER architecture and leads to delayed onset of senescence. In summary, we show for the first time a mutual molecular link between ER stress response and replicative senescence leading to phenotypic changes of non-malignant ovarian surface epithelium.

• Klíčová slova
• Endoplasmic reticulum stress, Ovarian surface epithelium, Senescence, Tauroursodeoxycholic acid, Unfolded protein response,
• MeSH
• down regulace účinky léků   MeSH
• epitel účinky léků   patologie   ultrastruktura   MeSH
• kyselina taurochenodeoxycholová farmakologie   MeSH
• messenger RNA genetika   metabolismus   MeSH
• myši MeSH
• ovarium patologie   MeSH
• stárnutí buněk účinky léků   MeSH
• stres endoplazmatického retikula účinky léků   MeSH
• tunikamycin farmakologie   MeSH
• upregulace účinky léků   MeSH
• zkracování telomer účinky léků   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• kyselina taurochenodeoxycholová MeSH
• messenger RNA MeSH
• tunikamycin MeSH
• ursodoxicoltaurine MeSH Prohlížeč

BRAFV600E mutations occur in ∼10% of colorectal cancer cases, are associated with poor survival, and have limited responses to BRAF/MEK inhibition with or without EGFR inhibition. There is an unmet need to understand the biology of poor prognostic BRAFMT colorectal cancer. We have used differential gene expression and pathway analyses of untreated stage II and stage III BRAFMT (discovery set: n = 31; validation set: n = 26) colorectal cancer, and an siRNA screen to characterize the biology underpinning the BRAFMT subgroup with poorest outcome. These analyses identified the unfolded protein response (UPR) as a novel and druggable pathway associated with the BRAFMT colorectal cancer subgroup with poorest outcome. We also found that oncogenic BRAF drives endoplasmic reticulum (ER) stress and UPR pathway activation through MEK/ERK. Furthermore, inhibition of GRP78, the master regulator of the UPR, using siRNA or small molecule inhibition, resulted in acute ER stress and apoptosis, in particular in BRAFMT colorectal cancer cells. In addition, dual targeting of protein degradation using combined Carfilzomib (proteasome inhibitor) and ACY-1215 (HDAC6-selective inhibitor) treatment resulted in marked accumulation of protein aggregates, acute ER stress, apoptosis, and therapeutic efficacy in BRAFMT in vitro and xenograft models. Mechanistically, we found that the apoptosis following combined Carfilzomib/ACY-1215 treatment is mediated through increased CHOP expression. Taken together, our findings indicate that oncogenic BRAF induces chronic ER stress and that inducers of acute ER stress could be a novel treatment strategy for poor prognostic BRAFMT colorectal cancer. Mol Cancer Ther; 17(6); 1280-90. ©2018 AACR.

• MeSH
• antitumorózní látky farmakologie   MeSH
• apoptóza účinky léků   genetika   MeSH
• biologické modely MeSH
• chaperon endoplazmatického retikula BiP MeSH
• inhibitory proteinkinas farmakologie   MeSH
• kolorektální nádory farmakoterapie   genetika   metabolismus   mortalita   MeSH
• kyseliny hydroxamové farmakologie   MeSH
• lidé MeSH
• MAP kinasový signální systém MeSH
• mutace * MeSH
• nádorové biomarkery MeSH
• nádorové buněčné linie MeSH
• oligopeptidy farmakologie   MeSH
• prognóza MeSH
• proteiny tepelného šoku genetika   metabolismus   MeSH
• proteosyntéza MeSH
• protoonkogenní proteiny B-Raf antagonisté a inhibitory   genetika   metabolismus   MeSH
• pyrimidiny farmakologie   MeSH
• signální dráha UPR účinky léků   MeSH
• signální transdukce účinky léků   MeSH
• stres endoplazmatického retikula účinky léků   genetika   MeSH
• transkripční faktor CHOP genetika   metabolismus   MeSH
• viabilita buněk účinky léků   genetika   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• antitumorózní látky MeSH
• carfilzomib MeSH Prohlížeč
• chaperon endoplazmatického retikula BiP MeSH
• DDIT3 protein, human MeSH Prohlížeč
• HSPA5 protein, human MeSH Prohlížeč
• inhibitory proteinkinas MeSH
• kyseliny hydroxamové MeSH
• nádorové biomarkery MeSH
• oligopeptidy MeSH
• proteiny tepelného šoku MeSH
• protoonkogenní proteiny B-Raf MeSH
• pyrimidiny MeSH
• ricolinostat MeSH Prohlížeč
• transkripční faktor CHOP MeSH

OBJECTIVES: To assess the potential of second-generation proteasome inhibition by carfilzomib and its combination with the human immunodeficiency virus (HIV) protease inhibitors (HIV-PIs) lopinavir and nelfinavir in vitro for improved treatment of clear cell renal cell cancer (ccRCC). MATERIALS AND METHODS: Cytotoxicity, reactive oxygen species (ROS) production, and unfolded protein response (UPR) activation of proteasome inhibitors, HIV-PIs, and their combination were assessed in three cell lines and primary cells derived from three ccRCC tumours by MTS assay, flow cytometry, quantitative reverse transcriptase-polymerase chain reaction and western blot, respectively. Proteasome activity was determined by activity based probes. Flow cytometry was used to assess apoptosis by annexin V/propidium iodide assay and ATP-binding cassette sub-family B member 1 (ABCB1) activity by MitoTracker™ Green FM efflux assay (Thermo Fisher Scientific, MA, USA). RESULTS: Lopinavir and nelfinavir significantly increased the cytotoxic effect of carfilzomib in all cell lines and primary cells. ABCB1 efflux pump inhibition, induction of ROS production, and UPR pre-activation by lopinavir were identified as underlying mechanisms of this strong synergistic effect. Combined treatment led to unresolved protein stress, increased activation of pro-apoptotic UPR pathway, and a significant increase in apoptosis. CONCLUSION: The combination of the proteasome inhibitor carfilzomib and the HIV-PIs lopinavir and nelfinavir has a strong synergistic cytotoxic activity against ccRCCin vitro at therapeutically relevant drug concentrations. This effect is most likely explained by synergistic UPR triggering and ABCB1-modulation caused by HIV-PIs. Our findings suggest that combined treatment of second-generation proteasome inhibitors and HIV-PIs should be investigated in patients with metastatic RCC within a clinical trial.

• Klíčová slova
• #KCSM, #KidneyCancer, HIV-protease inhibitors, bortezomib, carfilzomib, lopinavir, proteasome inhibitors, renal cell cancer,
• MeSH
• antitumorózní látky terapeutické užití   MeSH
• chemorezistence MeSH
• inhibitory HIV-proteasy terapeutické užití   MeSH
• inhibitory proteasomu terapeutické užití   MeSH
• karcinom z renálních buněk farmakoterapie   MeSH
• lidé MeSH
• Lopinavir terapeutické užití   MeSH
• nádorové buněčné linie MeSH
• nádory ledvin farmakoterapie   MeSH
• nelfinavir terapeutické užití   MeSH
• stres endoplazmatického retikula účinky léků   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• antitumorózní látky MeSH
• inhibitory HIV-proteasy MeSH
• inhibitory proteasomu MeSH
• Lopinavir MeSH
• nelfinavir MeSH

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.

• Klíčová slova
• Apoptosis, Calcium, Cancer, ER-stress, Melatonin, Reactive oxygen species,
• MeSH
• apoptóza účinky léků   MeSH
• cytosol metabolismus   MeSH
• fluorescenční mikroskopie MeSH
• inositol-1,4,5-trisfosfát - receptory antagonisté a inhibitory   genetika   MeSH
• lidé MeSH
• malá interferující RNA metabolismus   MeSH
• melatonin toxicita   MeSH
• nádorové buněčné linie MeSH
• pumpa pro výměnu sodíku a vápníku antagonisté a inhibitory   genetika   metabolismus   MeSH
• reaktivní formy kyslíku metabolismus   MeSH
• RNA interference MeSH
• stres endoplazmatického retikula účinky léků   MeSH
• transkripční faktor CHOP genetika   metabolismus   MeSH
• vápník metabolismus   MeSH
• XBP1 genetika   metabolismus   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• inositol-1,4,5-trisfosfát - receptory MeSH
• malá interferující RNA MeSH
• melatonin MeSH
• pumpa pro výměnu sodíku a vápníku MeSH
• reaktivní formy kyslíku MeSH
• sodium-calcium exchanger 1 MeSH Prohlížeč
• transkripční faktor CHOP MeSH
• vápník MeSH
• Xbp1 protein, mouse MeSH Prohlížeč
• XBP1 MeSH

Tyrosine kinases inhibitors (TKi) represent a relatively novel class of anticancer drugs that target cellular pathways overexpressed in certain types of malignancies, such as chronic myeloid leukaemia (CML). Nilotinib, ponatinib and imatinib exhibit cardiotoxic and vascular effects. In this study, we focused on possible cardiotoxicity of nilotinib using H9c2 cells as a suitable cell model. We studied role of endoplasmic reticulum (ER) stress and apoptosis in nilotinib toxicity using a complex approach. Nilotinib impaired mitochondrial function and induced formation of ROS under clinically relevant concentrations. In addition, ability of nilotinib to induce ER stress has been shown. These events result in apoptotic cell death. All these mechanisms contribute to cytotoxic effect of the drug. In addition, involvement of ER stress in nilotinib toxicity may be important in co-treatment with pharmaceuticals affecting ER and ER stress, e.g. beta-blockers or sartans, and should be further investigated.

• MeSH
• buněčná smrt účinky léků   fyziologie   MeSH
• buněčné linie MeSH
• kardiomyocyty účinky léků   fyziologie   MeSH
• krysa rodu Rattus MeSH
• pyrimidiny toxicita   MeSH
• stres endoplazmatického retikula účinky léků   fyziologie   MeSH
• tyrosinkinasy * metabolismus   MeSH
• viabilita buněk účinky léků   fyziologie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• nilotinib MeSH Prohlížeč
• pyrimidiny MeSH
• tyrosinkinasy * MeSH

Bcl2 and IAP families are anti-apoptotic proteins deregulated in multiple myeloma (MM) cells. Pharmacological inhibition of each of these families has shown significant activity only in subgroups of MM patients. Here, we have examined a broad-spectrum Bcl2 family inhibitor Obatoclax (OBX) in combination with a Smac mimetic LCL161 in MM cell lines and patient cells. LCL161/OBX combination induced synergistic cytotoxicity and anti-proliferative effects on a broad range of human MM cell lines. The cytotoxicity was mediated through inhibition of the IAPs, activation of caspases and up regulation of the pro-apoptotic proteins Bid, Bim, Puma and Noxa by the drug combination. In addition, we observed that OBX caused ER stress and activated the Unfolded Protein Response (UPR) leading to drug resistance. LCL161, however inhibited spliced Xbp-1, a pro-survival factor. In addition, we observed that OBX increased GRP78 localization to the cell surface, which then induced PI3K dependent Akt activation and resistance to cell death. LCL161 was able to block OBX induced Akt activation contributing to synergistic cell death. Our results support clinical evaluation of this combination strategy in relapsed refractory MM patients.

• Klíčová slova
• Bcl-2, GRP78, IAP, apoptosis, myeloma,
• MeSH
• antitumorózní látky farmakologie   terapeutické užití   MeSH
• apoptóza účinky léků   MeSH
• chaperon endoplazmatického retikula BiP MeSH
• chemorezistence MeSH
• down regulace MeSH
• fosfatidylinositol-3-kinasy metabolismus   MeSH
• fosforylace MeSH
• indoly MeSH
• intracelulární signální peptidy a proteiny agonisté   MeSH
• kaspasy metabolismus   MeSH
• lidé MeSH
• lokální recidiva nádoru farmakoterapie   patologie   MeSH
• mitochondriální proteiny agonisté   MeSH
• mnohočetný myelom farmakoterapie   patologie   MeSH
• nádorové buněčné linie MeSH
• proteiny regulující apoptózu MeSH
• proteiny tepelného šoku metabolismus   MeSH
• protokoly antitumorózní kombinované chemoterapie farmakologie   terapeutické užití   MeSH
• protoonkogenní proteiny c-akt metabolismus   MeSH
• protoonkogenní proteiny c-bcl-2 antagonisté a inhibitory   metabolismus   MeSH
• pyrroly farmakologie   terapeutické užití   MeSH
• signální dráha UPR účinky léků   MeSH
• stres endoplazmatického retikula účinky léků   MeSH
• synergismus léků MeSH
• thiazoly farmakologie   terapeutické užití   MeSH
• upregulace MeSH
• XBP1 metabolismus   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• antitumorózní látky MeSH
• BCL2 protein, human MeSH Prohlížeč
• chaperon endoplazmatického retikula BiP MeSH
• DIABLO protein, human MeSH Prohlížeč
• HSPA5 protein, human MeSH Prohlížeč
• indoly MeSH
• intracelulární signální peptidy a proteiny MeSH
• kaspasy MeSH
• LCL161 MeSH Prohlížeč
• mitochondriální proteiny MeSH
• obatoclax MeSH Prohlížeč
• proteiny regulující apoptózu MeSH
• proteiny tepelného šoku MeSH
• protoonkogenní proteiny c-akt MeSH
• protoonkogenní proteiny c-bcl-2 MeSH
• pyrroly MeSH
• thiazoly MeSH
• XBP1 protein, human MeSH Prohlížeč
• XBP1 MeSH

UNLABELLED: 9-Norbornyl-6-chloropurine (NCP) is a representative of a series of antienteroviral bicycle derivatives with selective cytotoxicity towards leukemia cell lines. In this work we explored the mechanism of the antileukemic activity of NCP in T-cell lymphoblast cells (CCRF-CEM). Specifically, we searched for a potential link between its ability to induce cell death on the one hand and to modulate intracellular glutathione (GSH) that is necessary to its metabolic transformation via glutathione-S-transferase on the other hand. We have observed that GSH levels decreased rapidly in NCP-treated cells. Despite a complete regeneration following 24h of incubation with NCP, this profound drop in cellular GSH content triggered ER stress, ROS production and lipid peroxidation leading to the loss of mitochondrial membrane potential (MMP). These events induced concentration-dependent cell cycle arrest in G2/M phase and apoptosis. Both MMP loss and apoptosis were reversed by sulfhydryl-containing compounds (GSH, N-acetyl-l-cysteine). Furthermore, we have also shown that NCP-induced GSH decrease activated the Nrf2 pathway and its downstream targets NAD(P)H: quinone oxidoreductase (NQO-1) and glutamate cysteine ligase modifier subunit (GCLm), thus explaining the fast restoration of GSH pool and ROS decrease. Importantly, we confirmed that the cell death-inducing properties of the compounds were co-dependent on their ability to diminish cellular GSH level by analyzing the relationships between the GSH-depleting potency and cytotoxicity in a series of other norbornylpurine analogs. Altogether, the results demonstrated that in CCRF-CEM cells NCP triggered apoptosis through GSH depletion-associated oxidative and ER stress and mitochondrial depolarization.

• Klíčová slova
• Apoptosis, Glutathione, Mitochondrial membrane potential, Norbornylpurines, Nrf-2, Reactive oxygen species, Unfolded protein response,
• MeSH
• apoptóza účinky léků   MeSH
• glutamátcysteinligasa genetika   MeSH
• glutathion metabolismus   MeSH
• glutathiontransferasa genetika   MeSH
• leukemie T-buněčná farmakoterapie   genetika   metabolismus   patologie   MeSH
• lidé MeSH
• mitochondrie účinky léků   patologie   MeSH
• NAD(P)H dehydrogenasa (chinon) genetika   MeSH
• oxidační stres účinky léků   MeSH
• peroxidace lipidů účinky léků   MeSH
• puriny aplikace a dávkování   MeSH
• reaktivní formy kyslíku metabolismus   MeSH
• regulace genové exprese u leukemie účinky léků   MeSH
• stres endoplazmatického retikula účinky léků   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• 9-norbornyl-6-chloropurine MeSH Prohlížeč
• GCLM protein, human MeSH Prohlížeč
• glutamátcysteinligasa MeSH
• glutathion MeSH
• glutathiontransferasa MeSH
• NAD(P)H dehydrogenasa (chinon) MeSH
• NQO1 protein, human MeSH Prohlížeč
• puriny MeSH
• reaktivní formy kyslíku MeSH