Renin and angiotensinogen expression and functions in growth and apoptosis of human glioblastoma

Abstract

The expression and function in growth and apoptosis of the renin -angiotensin system (RAS) was evaluated in human glioblastoma. Renin and angiotensinogen (AGT) mRNAs and proteins were found by in situ hybridisation and immunohistochemistry in glioblastoma cells. Angiotensinogen was present in glioblastoma cystic fluids. Thus, human glioblastoma cells produce renin and AGT and secrete AGT. Human glioblastoma and glioblastoma cells expressed renin, AGT, renin receptor, AT 2 and/or AT 1 mRNAs and proteins determined by RT -PCR and/or Western blotting, respectively. The function of the RAS in glioblastoma was studied using human glioblastoma cells in culture. Angiotensinogen, des(Ang I)AGT, tetradecapaptide renin substrate (AGT1 -14), Ang I, Ang II or Ang III, added to glioblastoma cells in culture, did not modulate their proliferation, survival or death. Angiotensin-converting enzyme inhibitors did not diminish glioblastoma cell proliferation. However, the addition of selective synthetic renin inhibitors to glioblastoma cells decreased DNA synthesis and viable tumour cell number, and induced apoptosis. This effect was not counterbalanced by concomitant addition of Ang II. In conclusion, the complete RAS is expressed by human glioblastomas and glioblastoma cells in culture. Inhibition of renin in glioblastoma cells may be a potential approach to control glioblastoma cell proliferation and survival, and glioblastoma progression in combination therapy.

Nuclear-delimited Angiotensin Receptor-mediated Signaling Regulates Cardiomyocyte Gene Expression

“…Lipid-soluble renin inhibitors and angiotensin converting enzyme inhibitor prodrugs are particularly effective in inhibiting ATR-related glioblastoma (41) and neuroblastoma (42) cell growth, pointing to the potential importance of blocking intracellular Ang-II signaling. Further information about the nature, role, and significance of cardiomyocyte nuclear ATRs should contribute to the development of rationally based intracrine pharmacology for cardiac remodeling prevention.…”

Genetic reprogramming of tumor cells by zinc finger transcription factors

“…These tumors are characterized by local invasion resulting in poor prognosis. AGT is a precursor of AgtII, a cellsignaling molecule associated with a variety of disorders, such as cardiovascular remodeling and cancer (18)(19)(20). IL-13R␣1 is a receptor for IL-13 and IL-4 and has been shown to mediate signaling processes that result in activation of the Jak1-STAT pathway.…”

Functionalized Pyrrolidines Inhibit α-Mannosidase Activity and Growth of Human Glioblastoma and Melanoma Cells

“…Therefore novel strategies, which must be able to reverse tumor resistance to chemotherapeutic agents, have to be envisioned to treat these cancers. We have previously shown that molecules unrelated to conventional therapeutic agents, such as the drugs targeting the endothelin 16,17 and the renin-angiotensin 18 systems, or carbohydrate analogues, 19 may be of some interest. In this context, agents able to modify the glycosylation pathways of tumor cells may be particularly valuable.…”