Inositol hexaphosphate represses telomerase activity and translocates TERT from the nucleus in mouse and human prostate cancer cells via the deactivation of Akt and PKC{alpha}
- Department of Biochemistry, Molecular and Cellular Biology, Georgetown University Medical Center, 3900 Reservoir Road, NW, Washington, DC 20057 (United States)
Inositol hexaphosphate (IP6) has anti-proliferative effects on a variety of cancer cells, including prostate cancer. However, the molecular mechanism of anti-proliferative effects of IP6 is not entirely understood. Since the activation of telomerase is crucial for cells to gain immortality and proliferation ability, we examined the role of IP6 in the regulation of telomerase activity in prostate cancer cells. Here, we show that IP6 represses telomerase activity in mouse and human prostate cancer cells dose-dependently. In addition, IP6 prevents the translocation of TERT to the nucleus. Since phosphorylation of TERT by Akt and/or PKC{alpha} is necessary for nuclear translocation, we examined phosphorylation of Akt and PKC{alpha} after IP6 treatments. Our results show that IP6 inhibits phosphorylation of Akt and PKC{alpha}. These results show for the first time that IP6 represses telomerase activity in prostate cancer cells by posttranslational modification of TERT via the deactivation of Akt and PKC{alpha}.
- OSTI ID:
- 20854554
- Journal Information:
- Biochemical and Biophysical Research Communications, Vol. 349, Issue 4; Other Information: DOI: 10.1016/j.bbrc.2006.09.002; PII: S0006-291X(06)02015-8; Copyright (c) 2006 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); ISSN 0006-291X
- Country of Publication:
- United States
- Language:
- English
Similar Records
Tamoxifen inhibits tumor cell invasion and metastasis in mouse melanoma through suppression of PKC/MEK/ERK and PKC/PI3K/Akt pathways
Activation of Telomerase by Ionizing Radiation: Differential Response to the Inhibition of DNA Double-Strand Break Repair by Abrogation of Poly(ADP-ribosyl)ation, by LY294002, or by Wortmannin