A gonadotropin-releasing hormone-II antagonist induces autophagy of prostate cancer cells

Title
A gonadotropin-releasing hormone-II antagonist induces autophagy of prostate cancer cells
Authors
김동기양지숙Kaushik Maiti황종익김경진신동승안영희이철주강병철권혁방전준성재영
Keywords
GnRH-II antagonist; prostate cancer; autophagy; reactive oxygen species; mitochondria
Issue Date
2009-02
Publisher
Cancer research : the official organ of the American Association for Cancer Research, Inc
Citation
VOL 69, NO 3, 923-931
Abstract
Gonadotropin-releasing hormone-I (GnRH-I) is known to directly regulate prostate cancer cell proliferation. However, the role of GnRH-II in prostate cancer is unclear. Here, we investigated the effect of the GnRH-II antagonist trptorelix-1 (Trp-1) on growth of PC3 prostate cancer cells. Trp-1 induced growth inhibition of PC3 cells in vitro and inhibited growth of PC3 cells xenografted into nude mice. FITC-N3, an FITCconjugated Trp-1analogue , was largely present in the mitochondria of prostate cancer cells, but not in other cells that are not derived from the prostate. Trp-1–induced PC3 growth inhibition was associated with decreased mitochondrial membrane potential and increased levels of mitochondrial and cytosolic reactive oxygen species (ROS). Growth inhibition was partially prevented by cotreating cells with Nacetyl cysteine, an antioxidant. Cytochrome c release and caspase-3 activation were not detected in Trp-1–treated cells. However, Trp-1induced autophagosome formation, as seen by increased LysoTracker staining and recruitment of microtubule- associated protein 1light chain 3 to these new lysosomal compartments. Trp-1–induced autophagy was accompanied by decreased AKT phosphorylation and increased c-Jun NH2 terminal kinase phosphorylation, two events known to be linked to autophagy. Taken together, these data suggest that Trp-1directly induces mitochondrial dysfunction and ROS increase, leading to autophagy of prostate cancer cells. GnRHII antagonists may hold promise in the treatment of prostate cancer.
URI
http://pubs.kist.re.kr/handle/201004/35500
ISSN
0008-5472
Appears in Collections:
KIST Publication > Article
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