Inhibition of cellular growth and induction of apoptosis in pituitary adenoma cell lines by the protein kinase C inhibitor hypericin: potential therapeutic application

Update Item Information
Publication Type Journal Article
School or College School of Medicine
Department Neurosurgery
Creator Couldwell, William T.
Other Author Hamilton, H. Bruce; Hinton, David R.; Law, Ronald E.; Gopalakrishna, Rayudu; Su, Yu Zhang; Chen, Zhen-Hai; Weiss, Martin H.
Title Inhibition of cellular growth and induction of apoptosis in pituitary adenoma cell lines by the protein kinase C inhibitor hypericin: potential therapeutic application
Date 1996
Description Protein kinase C (PKC) is an enzyme involved in the regulation of cellular growth, proliferation, and differentiation in a number of tissues including the anterior pituitary, in which it is also believed to play a role in hormone secretion. Protein kinase C activity and expression have been found to be greater in adenomatous pituitary cells than in normal human and rat pituitary cells and higher in invasive pituitary tumor cells than in noninvasive ones. Inhibition of PKC activity has been shown in a variety of tumor cells to inhibit growth in a dose-related fashion. The purpose of the current study was to determine whether hypericin, a potent inhibitor of PKC activity that may be administered clinically, alters the growth and proliferation in established pituitary adenoma lines and to determine if inhibition of PKC activity induces apoptosis, as reported in some other tumor cell types. Two established pituitary adenoma cell lines, AtT-20 and GH4C1, were treated with hypericin in tissue culture for defined periods following passage. Inhibition of growth was found to be dose dependent in all three cell lines in low micromolar concentrations of hypericin, as determined by viable cell counts, methylthiotetrazole assay, and [3H]thymidine uptake studies. Concentrations of hypericin as low as 100 nM also induced apoptosis in these established lines, whereas treatment of normal human fibroblasts with a concentration of 10 mM failed to induce apoptosis. The potential use of hypericin in the therapy of pituitary adenomas warrants additional in vitro investigations with the aim of later moving toward therapeutic trials in selected patients in whom surgical or medical therapy has failed.
Type Text
Publisher American Association of Neurological Surgeons (AANS)
Volume 85
Issue 2
First Page 329
Last Page 334
Subject Apoptosis; Hypericin; Pituitary adenoma; Protein kinase C
Subject LCSH Protein kinases; Apoptosis; Adenoma -- Treatment
Subject MESH Pituitary Neoplasms; Apoptosis; Adenoma
Language eng
Bibliographic Citation Hamilton, H. B., Hinton, D. R., Law, R. E., Gopalakrishna, R., Su, Y. Z., Chen, Z. H., Weiss, M. H., & Couldwell, W. T. (1996). Inhibition of cellular growth and induction of apoptosis in pituitary adenoma cell lines by the protein kinase C inhibitor hypericin: potential therapeutic application. Journal of Neurosurgery, 85(2), 329-34.
Rights Management (c) American Association of Neurological Surgeons
Format Medium application/pdf
Format Extent 410,312 bytes
Identifier ir-main,12556
ARK ark:/87278/s696026w
Setname ir_uspace
ID 707090
Reference URL https://collections.lib.utah.edu/ark:/87278/s696026w
Back to Search Results