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

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Abstract
✓ 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 defi...