Induction of the endoplasmic reticulum stress protein GADD153/CHOP by capsaicin in prostate PC-3 cells: A microarray study

Sánchez, Ana M.; Martı́nez-Botas, Javier; Malagarie‐Cazenave, Sophie; Olea, Nuria; Vara, Diana; Lasunción, Miguel A.; Díaz‐Laviada, Inés

doi:10.1016/j.bbrc.2008.05.138

Cited by 65 publications

(40 citation statements)

References 19 publications

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“…ER membrane associated caspase 12 is also implicated in the activation of apoptosis through direct activation of caspase 3 or by caspase 9. CHOP/GADD153, sensor of endoplasmic reticulum stress, is highly up-regulated during ER stress [18,19]. In our studies, caspase 12 activation was observed to be associated with enhanced intracellular calcium levels together with increased mRNA and protein levels of CHOP/GADD153 [20,21].…”

Section: Er Stress and Apoptotic Signalingmentioning

confidence: 78%

Role of Endoplasmic Reticulum Stress and Unfolded Protein Responses in Health and Diseases

2015

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Endoplasmic reticulum (ER) is the site of protein synthesis, protein folding, maintainance of calcium homeostasis, synthesis of lipids and sterols. Genetic or environmental insults can alter its function generating ER stress. ER senses stress mainly by three stress sensor pathways, namely protein kinase R-like endoplasmic reticulum kinase-eukaryotic translation-initiation factor 2a, inositol-requiring enzyme 1a-X-box-binding protein 1 and activating transcription factor 6-CREBH, which induce unfolded protein responses (UPR) after the recognition of stress. Recent studies have demonstrated that ER stress and UPR signaling are involved in cancer, metabolic disorders, inflammatory diseases, osteoporosis and neurodegenerative diseases. However, the precise knowledge regarding involvement of ER stress in different disease processes is still debatable. Here we discuss the possible role of ER stress in various disorders on the basis of existing literature. An attempt has also been made to highlight the present knowledge of this field which may help to elucidate and conjure basic mechanisms and novel insights into disease processes which could assist in devising better future diagnostic and therapeutic strategies.

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Section: Er Stress and Apoptotic Signalingmentioning

confidence: 78%

Role of Endoplasmic Reticulum Stress and Unfolded Protein Responses in Health and Diseases

2015

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“…Functional annotation clustering using DAVID software (12) showed that 17 of the up-regulated genes function as activators of apoptosis (Table S2). It has been shown that these genes induce growth arrest and apoptosis in cancer cells (13)(14)(15). Using AnnexinV binding assays and flow cytometry analysis of DU145 cells transfected with GFP-tagged GFP-tagged C/EBPhomologous protein (CHOP), FBJ murine osteosarcoma viral (v-fos) oncogene homolog (FOS) and nuclear receptor subfamily 4, group A, member 2 (NR4A2), we confirmed that overexpression of these proteins induced apoptosis in DU145 cells, whereas GFP alone did not affect cell survival ( Fig.…”

Section: St3-h2a2mentioning

confidence: 99%

STAT3 suppresses transcription of proapoptotic genes in cancer cells with the involvement of its N-terminal domain

Timofeeva¹,

Tarasova

Zhang³

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

122

120

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Activation of STAT3 in cancers leads to gene expression promoting cell proliferation and resistance to apoptosis, as well as tumor angiogenesis, invasion, and migration. In the characterization of effects of ST3-H2A2, a selective inhibitor of the STAT3 N-terminal domain (ND), we observed that the compound induced apoptotic death in cancer cells associated with robust activation of proapoptotic genes. Using ChIP and tiling human promoter arrays, we found that activation of gene expression in response to ST3-H2A2 is accompanied by altered STAT3 chromatin binding. Using inhibitors of STAT3 phosphorylation and a dominant-negative STAT3 mutant, we found that the unphosphorylated form of STAT3 binds to regulatory regions of proapoptotic genes and prevents their expression in tumor cells but not normal cells. siRNA knockdown confirmed the effects of ST3-HA2A on gene expression and chromatin binding to be STAT3 dependent. The STAT3-binding region of the C/EBP-homologous protein (CHOP) promoter was found to be localized in DNaseI hypersensitive site of chromatin in cancer cells but not in nontransformed cells, suggesting that STAT3 binding and suppressive action can be chromatin structure dependent. These data demonstrate a suppressive role for the STAT3 ND in the regulation of proapoptotic gene expression in cancer cells, providing further support for targeting STAT3 ND for cancer therapy.H3K9me3 | peptide inhibitor | prostate cancer | transcription factor S TAT3, a member of the STAT family, is a key signaling protein that transduces extracellular signals to the nucleus and regulates transcription of genes (1). Following ligand stimulation, STAT3 is phosphorylated on Y705 tyrosine residue, dimerizes, and translocates to the nucleus to bind its cognate DNA-response elements, activating gene transcription (1). Constitutively activated STAT3 mediates deregulated growth, survival, and angiogenesis (2, 3). STAT3 is widely recognized as a potential drug target for cancer therapy, and various approaches, including targeting of upstream tyrosine kinases and direct inhibitors of STAT3 dimerization, have been advanced to inhibit STAT3 signaling in cancers (4). However, unphosphorylated STAT3 (U-STAT3) has also been shown to influence gene transcription, both in response to cytokines and in cancer cells, albeit by mechanisms that are distinct from those activated by phosphorylated STAT3 (5). We have developed a highly selective inhibitor of STAT3 ND, ST3-Hel2A-2 (ST3-H2A2), that binds to the N-terminal domain (ND) and inhibits STAT3 signaling (6). STAT3 ND is involved in the interactions of two STAT dimers on neighboring sites to form a more stable tetramer and the interactions with histone-modifier proteins to induce changes in chromatin structure (reviewed in ref. 7). These complex interactions may greatly affect STAT3-dependent transcriptional activity, suggesting that the STAT3 ND mediates important regulatory functions of STAT3 in normal cells (8) and in cancer (9). ST3-H2A2 induces death in breast cancer cells MDA-MB-231 an...

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“…Blockage of expression of this gene significantly reduced capsaicin-induced cell death. 4 Capsaicin has shown activity in other cancer cell lines. It induced apoptosis of glioma cells, 5 hepatocellular carcinoma cells, 6 human esophagus epidermoid cells, 7 human leukemia cells 8 and human breast cancer cells.…”

Section: Discussionmentioning

confidence: 99%

Capsaicin may slow PSA doubling time: case report and literature review

Janković

Loblaw

Nam

2013

CUAJ

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Capsaicin is the main pungent component of chili peppers. Thisis the first case, to our knowledge, that describes prostatespecificantigen (PSA) stabilization in a patient with prostate cancer,who had biochemical failure after radiation therapy. A 66-year-old male underwent radiotherapy treatment for a T2b, Gleason7 (3+4) adenocarcinoma of the prostate, with a PSA level of13.3 ng/mL in April 2001. He had 3-dimensional conformal radiotherapyof 46 Gy in 23 fractions to the prostate and pelvis, and aprostate boost of 30 Gy in 15 fractions. Radiotherapy was completedin May 2001 and PSA nadired in January 2002 (0.57). Dueto the continued PSA rise, the patient was started on bicalutamide(50 mg orally, daily) and leuprolide acetate (1 dose of 22.5 mgintramuscularly) in July 2005 when PSA was 38.5 ng/mL. Due topoor tolerance of androgen ablation therapy, the patient discontinuedtreatment and started taking 2.5 mL of habaneros chilisauce, containing capsaicin, 1 to 2 times a week in April 2006.Prostate-specific antigen doubling time (PSAdt) increased from4 weeks before capsaicin to 7.3 months by October 2006. FromOctober 2006 until November 2007, the patient remained oncapsaicin (2.5 to 15 mL daily) and his PSA was stable (between11 to 14 ng/mL). By January 2008, his PSA rose to 22.3 and hehas maintained a PSAdt between 4 and 5 months, where it presentlyremains. Due to the patient’s continued PSA rise, he was restartedon bicalutamide (12.5 mg daily). Apart from PSA relapse, the patientremains free of signs or symptoms of recurrence.

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Induction of the endoplasmic reticulum stress protein GADD153/CHOP by capsaicin in prostate PC-3 cells: A microarray study

Cited by 65 publications

References 19 publications

Role of Endoplasmic Reticulum Stress and Unfolded Protein Responses in Health and Diseases

Role of Endoplasmic Reticulum Stress and Unfolded Protein Responses in Health and Diseases

STAT3 suppresses transcription of proapoptotic genes in cancer cells with the involvement of its N-terminal domain

Capsaicin may slow PSA doubling time: case report and literature review

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