15-Deoxy-Δ12,14-prostaglandin J2 induces apoptosis through activation of the CHOP gene in HeLa cells

Saito, Shôichi; Takahashi, Shouji; Takagaki, Nobumasa; Hirose, Tohru; Sakai, Toshiyuki

doi:10.1016/j.bbrc.2003.09.161

Cited by 22 publications

(21 citation statements)

References 16 publications

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“…Our data with mRNA measurement, promoter activity assay, and siRNA approach suggest that DR5 induction by 15dPGJ 2 in three colon cancer cell types occurs at the transcriptional level and is mediated by increasing CHOP gene transcription. These results are consistent with those reported in HeLa cells, where CHOP was increased by 15dPGJ 2 (22). In contrast, in PC3 cells, 15dPGJ 2 -induced DR5 expression did not occur through an increase in DR5 mRNA transcription but through mRNA stabilization (16).…”

Section: Discussionsupporting

confidence: 92%

“…These results suggest a differential mechanism, in addition to ROS and calcium, might be required to activate the CHOP gene in PC3 cells in a cooperative manner, and such regulation is specific to15dPGJ 2 but is not a general event for most ER stressors. Because a previous study showed the involvement of the C/EBP site and ER-stress element in activating the CHOP gene by 15dPGJ 2 in HeLa cells (22), we were interested in further dissecting the linkage between second messengers (ROS and calcium) and transcription factors in activating the CHOP gene in HCT116 and PC3 cells.…”

Section: Discussionmentioning

confidence: 99%

“…In human PC3 prostate cancer cells, 15dPGJ 2 was shown to up-regulate the DR5 protein through mRNA stabilization rather than gene transcription (16). Paradoxically, 15dPGJ 2 is capable of inducing CHOP gene in HeLa cells via activation of C/EBP and ER-stress element sites in the CHOP promoter (22). These unique and distinct results compared with other ER stress inducers sparked our interest in further investigating the molecular mechanisms underlying DR5 protein induction by 15dPGJ 2 in human HCT116 colon cancer cells.…”

Section: Introductionmentioning

confidence: 99%

“…Evidence indicates that activation of a CHOP-binding site on the DR5 promoter region accounts for DR5 gene transcription induced by MG132 (14), TM (20), and TG (9). 15dPGJ 2 is not only an endogenous agonist of PPAR-g (21) but also an ER stress inducer (22). Its effective induction of cell apoptosis resulting from ROS suggests its potential therapeutic value in anticancer therapy (23,24).…”

Section: Introductionmentioning

confidence: 99%

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15-deoxy-Δ12,14-prostaglandin J2 up-regulates death receptor 5 gene expression in HCT116 cells: involvement of reactive oxygen species and C/EBP homologous transcription factor gene transcription

Chi

Huang

et al. 2008

Molecular Cancer Therapeutics

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Although 15-deoxy-# 12,14 -prostaglandin J 2 (15dPGJ 2 ) was reported to up-regulate death receptor 5 (DR5) protein expression and sensitize TRAIL-induced cytotoxicity, its action mechanism remains unclear. Using HCT116 colon cancer cells, we found that sensitization of TRAIL-induced cytotoxicity by 15dPGJ 2 resulted from up-regulation of DR5 via gene transcription but was not associated with PPAR-; activation. Moreover, 15dPGJ 2 induced GRP78, XBP1, and C/EBP homologous transcription factor (CHOP) expression in HCT116 cells, confirming that 15dPGJ 2 is an endoplasmic reticulum stress inducer. Knockdown of the CHOP gene by siRNA attenuated DR5 up-regulation and the sensitized cytotoxicity in colon cancer HCT116 and SW480. With deletion plasmids of DR5 promoters, we found that the CHOP-binding site was involved in activating the DR5 gene by 15dPGJ 2 . A mechanistic study showed the contributions of reactive oxygen species (ROS) and intracellular calcium in CHOP and DR5 gene up-regulation. 15dPGJ 2 was also found to induce DR5 in two prostate cancer cell lines, LNCaP and PC3. Although in LNCaP DR5 up-regulation was accompanied by CHOP expression by 15dPGJ 2 , no significant increase in CHOP expression or DR5 promoter activity was observed in PC3 cells. Intriguingly, 15dPGJ 2 induced ROS and calcium production in PC3 cells. This inability to induce CHOP was not due to the p53-null in PC3 cells, as similar extents of increase in CHOP protein were found due to 15dPGJ 2 in both wild-type and p53-null HCT116 cells. In summary, the effect of up-regulation of DR5 by 15dPGJ 2 in colon cancer cells is independent of PPAR-; and p53 but relies on CHOP induction through gene transcription involving ROS and calcium. [Mol Cancer Ther 2008;7(10):3429 -40]

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

15-deoxy-Δ12,14-prostaglandin J2 up-regulates death receptor 5 gene expression in HCT116 cells: involvement of reactive oxygen species and C/EBP homologous transcription factor gene transcription

Chi

Huang

et al. 2008

Molecular Cancer Therapeutics

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“…Plasmid preparation, transient transfection and luciferase assay DR5 and CHOP promoters and deletion mutants were generated as described previously (Yoshida et al, 2001;Saito et al, 2003;Shiraishi et al, 2005). Luciferase constructs of survivin promoter (pLuc-Surv/À1430; pLuc-Surv/À3000; pLuc-Surv/À6430) and its empty vector (pLuc) were a kind gift from Dr Dario Altieri (University of Massachusetts Medical School, Worcester, MA, USA).…”

Section: Immunoblot Analysismentioning

confidence: 99%

Mechanisms of enhancement of TRAIL tumoricidal activity against human cancer cells of different origin by dipyridamole

et al. 2008

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Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has emerged as an attractive cytokine that selectively targets cancer cells, however its efficacy has been challenged by a number of resistance mechanisms. Therefore, the current study investigated the potential of dipyridamole to enhance TRAIL efficacy and the probable underlying mechanisms. Dipyridamole dramatically sensitized p53-mutant human cancer cell lines: SW480, MG63 and DU145, to the antitumor activity of TRAIL, as evidenced by enabling TRAIL to efficiently cleave initiator and executioner caspases. Although dipyridamole upregulated both DR4 and DR5 and increased their cell surface expression, RNA interference revealed a preferential dependence on DR5. Moreover, dipyridamole inhibited survivin expression and its important consequences were confirmed by small interfering RNA. Mechanistically, dipyridamole induced transcriptional shutdown of survivin expression accompanying G 1 arrest that was characterized by downregulation of D-type cyclins and cdk6. In addition, a transcriptional mechanism powered by CCAAT/enhancer-binding protein (C/EBP) homologous protein (CHOP) induction was responsible for DR5 upregulation by dipyridamole. Importantly, dipyridamole-induced enhancement of TRAIL efficacy and alterations of protein expression were independent of either protein kinase A or protein kinase G. In conclusion, findings of the present study described novel mechanisms of dipyridamole action and highlighted its promising use as a potential enhancer of TRAIL efficacy.

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Anandamide‐induced endoplasmic reticulum stress and apoptosis are mediated by oxidative stress in non‐melanoma skin cancer: Receptor‐independent endocannabinoid signaling

Soliman

Dross

2015

Molecular Carcinogenesis

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Endocannabinoids are neuromodulatory lipids that regulate central and peripheral physiological functions. Endocannabinoids have emerged as effective antitumor drugs due to their ability to induce apoptosis in various cancer studies. The G-protein coupled cannabinoid receptors (CB1 and CB2) and the TRPV1 ion channel were reported to mediate the antiproliferative activity of endocannabinoids. However, receptor-independent effects also account for their activity. Our previous studies showed that the antiproliferative activity of anandamide (AEA) was regulated by cyclooxygenase-2 (COX-2) via induction of endoplasmic reticulum (ER) stress. We also determined that AEA induced oxidative stress. However, the role of oxidative stress, the cannabinoid receptors, and TRPV1 in AEA-induced ER stress-apoptosis was unclear. Therefore, the current study examines the role of oxidative stress in ER stress-apoptosis and investigates whether this effect is modulated by CB1, CB2, or TRPV1. In non-melanoma skin cancer (NMSC) cells, AEA reduced the total intracellular level of glutathione and induced oxidative stress. To evaluate the importance of oxidative stress in AEA-induced cell death, the antioxidants, N-acetylcysteine (NAC) and Trolox, were utilized. Each antioxidant ameliorated the antiproliferative effect of AEA. Furthermore, Trolox inhibited AEA-induced CHOP10 expression and caspase 3 activity, indicating that oxidative stress was required for AEA-induced ER stress-apoptosis. On the other hand, selective blockade of CB1, CB2, and TRPV1 did not inhibit AEA-induced oxidative stress or ER stress-apoptosis. These findings suggest that AEA-induced ER stress-apoptosis in NMSC cells is mediated by oxidative stress through a receptor-independent mechanism. Hence, receptor-independent AEA signaling pathways may be targeted to eliminate NMSC. © 2015 Wiley Periodicals, Inc.

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15-Deoxy-Δ12,14-prostaglandin J2 induces apoptosis through activation of the CHOP gene in HeLa cells

Cited by 22 publications

References 16 publications

15-deoxy-Δ12,14-prostaglandin J2 up-regulates death receptor 5 gene expression in HCT116 cells: involvement of reactive oxygen species and C/EBP homologous transcription factor gene transcription

15-deoxy-Δ12,14-prostaglandin J2 up-regulates death receptor 5 gene expression in HCT116 cells: involvement of reactive oxygen species and C/EBP homologous transcription factor gene transcription

Mechanisms of enhancement of TRAIL tumoricidal activity against human cancer cells of different origin by dipyridamole

Anandamide‐induced endoplasmic reticulum stress and apoptosis are mediated by oxidative stress in non‐melanoma skin cancer: Receptor‐independent endocannabinoid signaling

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