Displaying all 3 publications

Abstract:
Sort:
  1. Yaacob NS, Nasir R, Norazmi MN
    Asian Pac J Cancer Prev, 2013;14(11):6761-7.
    PMID: 24377602
    The nuclear receptor, peroxisome proliferator-activated receptor gamma (PPARγ), is expressed in various cancer cells including breast, prostate, colorectal and cervical examples. An endogenous ligand of PPARγ, 15-deoxy-Δ12,14 prostaglandin J2 (PGJ2), is emerging as a potent anticancer agent but the exact mechanism has not been fully elucidated, especially in breast cancer. The present study compared the anticancer effects of PGJ2 on estrogen receptor alpha (ERα)-positive (MCF-7) and ERα-negative (MDA-MB-231) human breast cancer cells. Based on the reported signalling cross-talk between PPARγ and ERα, the effect of the ERα ligand, 17β-estradiol (E2) on the anticancer activities of PGJ2 in both types of cells was also explored. Here we report that PGJ2 inhibited proliferation of both MCF-7 and MDA-MB-231 cells by inducing apoptotic cell death with active involvement of mitochondria. The presence of E2 potentiated PGJ2-induced apoptosis in MCF-7, but not in MDA-MB-231 cells. The PPARγ antagonist, GW9662, failed to block PGJ2-induced activities but potentiated its effects in MCF-7 cells, instead. Interestingly, GW9662 also proved capable of inducing apoptotic cell death. It can be concluded that E2 enhances PPARγ-independent anticancer effects of PGJ2 in the presence of its receptor.
    Matched MeSH terms: Prostaglandin D2/analogs & derivatives*
  2. Tan BS, Kang O, Mai CW, Tiong KH, Khoo AS, Pichika MR, et al.
    Cancer Lett, 2013 Aug 9;336(1):127-39.
    PMID: 23612072 DOI: 10.1016/j.canlet.2013.04.014
    6-Shogaol has been shown to possess many antitumor properties including inhibition of cancer cell growth, inhibition of cancer metastasis, induction of apoptosis in cancer cells and induction of cancer cell differentiation. Despite its prominent antitumor effects, the direct molecular target of 6-shogaol has remained elusive. To identify the direct targets of 6-shogaol, a comprehensive antitumor profile of 6-shogaol (NSC752389) was tested in the NCI-60 cell line in an in vitro screen. The results show that 6-shogaol is COMPARE negative suggesting that it functions via a mechanism of action distinct from existing classes of therapeutic agents. Further analysis using microarray gene profiling and Connectivity Map analysis showed that MCF-7 cells treated with 6-shogaol display gene expression signatures characteristic of peroxisome proliferator activated receptor γ (PPARγ) agonists, suggesting that 6-shogaol may activate the PPARγ signaling pathway for its antitumor effects. Indeed, treatment of MCF-7 and HT29 cells with 6-shogaol induced PPARγ transcriptional activity, suppressed NFκB activity, and induced apoptosis in breast and colon cancer cells in a PPARγ-dependent manner. Furthermore, 6-shogaol is capable of binding to PPARγ with a binding affinity comparable to 15-delta prostaglandin J2, a natural ligand for PPARγ. Together, our findings suggest that the antitumor effects of 6-shogaol are mediated through activation of PPARγ and imply that activation of PPARγ might be beneficial for breast and colon cancer treatment.
    Matched MeSH terms: Prostaglandin D2/analogs & derivatives
  3. Rasheed ZB, Lee YS, Kim SH, Teoh T, MacIntyre DA, Bennett PR, et al.
    PMID: 36213265 DOI: 10.3389/fendo.2022.983924
    BACKGROUND: Prematurity is the leading cause of childhood death under the age of five. The aetiology of preterm birth is multifactorial; however, inflammation and infection are the most common causal factors, supporting a potential role for immunomodulation as a therapeutic strategy. 15-Deoxy-Delta-12,14-prostaglandin J2 (15dPGJ2) is an anti-inflammatory prostaglandin and has been shown to delay lipopolysaccharide (LPS) induced preterm labour in mice and improve pup survival. This study explores the immunomodulatory effect of 15dPGJ2 on the transcription factors NF-κB and AP-1, pro-inflammatory cytokines, and contraction associated proteins in human cultured myocytes, vaginal epithelial cell line (VECs) and primary amnion epithelial cells (AECs).

    METHODS: Cells were pre-incubated with 32µM of 15dPGJ2 and stimulated with 1ng/mL of IL-1β as an in vitro model of inflammation. Western immunoblotting was used to detect phosphorylated p-65 and phosphorylated c-Jun as markers of NF-κB and AP-1 activation, respectively. mRNA expression of the pro-inflammatory cytokines IL-6, IL-8, and TNF-α was examined, and protein expression of COX-2 and PGE2 were detected by western immunoblotting and ELISA respectively. Myometrial contractility was examined ex-vivo using a myograph.

    RESULTS: 15dPGJ2 inhibited IL-1β-induced activation of NF-κB and AP-1, and expression of IL-6, IL-8, TNF-α, COX-2 and PGE2 in myocytes, with no effect on myometrial contractility or cell viability. Despite inhibiting IL-1β-induced activation of NF-κB, expression of IL-6, TNF-α, and COX-2, 15dPGJ2 led to activation of AP-1, increased production of PGE2 and increased cell death in VECs and AECs.

    CONCLUSION: We conclude that 15dPGJ2 has differential effects on inflammatory modulation depending on cell type and is therefore unlikely to be a useful therapeutic agent for the prevention of preterm birth.

    Matched MeSH terms: Prostaglandin D2/analogs & derivatives
Related Terms
Filters
Contact Us

Please provide feedback to Administrator (afdal@afpm.org.my)

External Links