Inhibition of tubulogenesis and of carcinogen-mediated signaling in brain endothelial cells highlight the antiangiogenic properties of a mumbaistatin analog
- PMID: 20486934
- DOI: 10.1111/j.1747-0285.2010.00961.x
Inhibition of tubulogenesis and of carcinogen-mediated signaling in brain endothelial cells highlight the antiangiogenic properties of a mumbaistatin analog
Abstract
A better understanding of the metabolic adaptations of the vascular endothelial cells (EC) that mediate tumor vascularization would help the development of new drugs and therapies. Novel roles in cell survival and metabolic adaptation to hypoxia have been ascribed to the microsomal glucose-6-phosphate translocase (G6PT). While antitumorigenic properties of G6PT inhibitors such as chlorogenic acid (CHL) have been documented, those of the G6PT inhibitor and semi-synthetic analog AD4-015 of the polyketide mumbaistatin are not understood. In the present study, we evaluated the in vitro antiangiogenic impact of AD4-015 on human brain microvascular endothelial cells (HBMEC), which play an essential role as structural and functional components in tumor angiogenesis. We found that in vitro HBMEC migration and tubulogenesis were reduced by AD4-015 but not by CHL. The mumbaistatin analog significantly inhibited the phorbol 12-myristate 13-acetate (PMA)-induced matrix-metalloproteinase (MMP)-9 secretion and gene expression as assessed by zymography and RT-PCR. PMA-mediated cell signaling leading to cyclooxygenase (COX)-2 expression and IkappaB downregulation was also inhibited, further confirming AD4-015 as a cell signaling inhibitor in tumor promoting conditions. G6PT functions may therefore account for the metabolic flexibility that enables EC-mediated neovascularization. This process could be specifically targeted within the vasculature of developing brain tumors by G6PT inhibitors.
Similar articles
-
Propranolol adrenergic blockade inhibits human brain endothelial cells tubulogenesis and matrix metalloproteinase-9 secretion.Pharmacol Res. 2009 Nov;60(5):438-45. doi: 10.1016/j.phrs.2009.05.005. Epub 2009 May 23. Pharmacol Res. 2009. PMID: 19467330
-
Role of protein kinase C-dependent signaling pathways in the antiangiogenic properties of nafoxidine.Anticancer Res. 2004 May-Jun;24(3a):1737-43. Anticancer Res. 2004. PMID: 15274349
-
Statins inhibit cyclooxygenase-2 and matrix metalloproteinase-9 in human endothelial cells: anti-angiogenic actions possibly contributing to plaque stability.Cardiovasc Res. 2010 May 1;86(2):311-20. doi: 10.1093/cvr/cvp375. Epub 2009 Nov 27. Cardiovasc Res. 2010. PMID: 19946014
-
Modulating the hypoxia-inducible factor signaling pathway as a therapeutic modality to regulate retinal angiogenesis.Exp Eye Res. 2009 Nov;89(5):700-17. doi: 10.1016/j.exer.2009.06.013. Epub 2009 Jul 4. Exp Eye Res. 2009. PMID: 19580810
-
Silencing of the MT1-MMP/ G6PT axis suppresses calcium mobilization by sphingosine-1-phosphate in glioblastoma cells.FEBS Lett. 2008 Mar 5;582(5):799-804. doi: 10.1016/j.febslet.2008.01.061. Epub 2008 Feb 11. FEBS Lett. 2008. PMID: 18267120
Cited by
-
Resveratrol Targeting of Carcinogen-Induced Brain Endothelial Cell Inflammation Biomarkers MMP-9 and COX-2 is Sirt1-Independent.Drug Target Insights. 2012;6:1-11. doi: 10.4137/DTI.S9442. Epub 2012 Apr 11. Drug Target Insights. 2012. PMID: 22523472 Free PMC article.
-
A molecular signature for the G6PC3/SLC37A2/SLC37A4 interactors in glioblastoma disease progression and in the acquisition of a brain cancer stem cell phenotype.Front Endocrinol (Lausanne). 2023 Nov 16;14:1265698. doi: 10.3389/fendo.2023.1265698. eCollection 2023. Front Endocrinol (Lausanne). 2023. PMID: 38034009 Free PMC article.
-
G6PC indicated poor prognosis in cervical cancer and promoted cervical carcinogenesis in vitro and in vivo.Reprod Biol Endocrinol. 2022 Mar 11;20(1):50. doi: 10.1186/s12958-022-00921-6. Reprod Biol Endocrinol. 2022. PMID: 35277194 Free PMC article.
-
Low intracellular ATP levels exacerbate carcinogen-induced inflammatory stress response and inhibit in vitro tubulogenesis in human brain endothelial cells.J Inflamm Res. 2011;4:1-10. doi: 10.2147/JIR.S15880. Epub 2011 Jan 7. J Inflamm Res. 2011. PMID: 22096365 Free PMC article.
-
Metabolic rewiring in the promotion of cancer metastasis: mechanisms and therapeutic implications.Oncogene. 2020 Sep;39(39):6139-6156. doi: 10.1038/s41388-020-01432-7. Epub 2020 Aug 24. Oncogene. 2020. PMID: 32839493 Free PMC article. Review.
Publication types
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
Research Materials
Miscellaneous
