Abstract
The effects of butyrate and retinoic acid in combination with catecholamines or histamine on the HN-1 human head and neck squamous carcinoma cell line were investigated analysing cell proliferation, placental alkaline phosphatase (PLAP) activity, and relative cytokeratin content. Butyrate inhibited cell proliferation in agar, whereas retinoic acid induced a small inhibitory effect. Butyrate enhanced PLAP activity in a time related manner in contrast to retinoic acid, which had no significant effect. However, retinoic acid inhibited the efficacy of butyrate to induce PLAP activity. A synergistic enhancement of PLAP activity was demonstrated after treatment of butyrate pretreated cells with catecholamines or histamine. The beta-adrenergic antagonist propranolol partly inhibited the aforementioned enhancement of PLAP activity, whereas the alpha-adrenergic antagonist phentolamine further enhanced PLAP activity. Indirect labeling of keratins with a polyclonal antibody showed that cytokeratin content was enhanced by butyrate but not by retinoic acid. Further analysis of cytokeratin content using four monoclonal antibodies showed that labeling of cytokeratins (5 + 8) was increased by butyrate. PLAP activity could be modulated by a concerted action of either butyrate plus retinoic acid or butyrate plus catecholamines or histamine, indicating a possible role for PLAP in tumour cell proliferation.
Highlights
It was shown that cAMP-elevating agents like catecholamines, potentiated the action of retinoic acid in eliciting normal epithelial cell differentiation (Schiff & Moore, 1985)
The 4-methylumbelliferyl phosphate (4-MUP) was purified before use to remove traces of free 4MU
The effect of butyrate (0.5-2.5 mM) and retinoic acid (101 10-7 M) on the proliferation of HN-1 cells was monitored after a 3 day pretreatment of cells in the exponential growth phase or treatment during colony growth in soft agar
Summary
It was shown that cAMP-elevating agents like catecholamines, potentiated the action of retinoic acid in eliciting normal epithelial cell differentiation (Schiff & Moore, 1985). Catecholamines have other intriguing effects on cells, including regulation of cell division (Kennedy et al, 1985; Tutton & Barkla, 1980), induction of alkaline phosphatase (Mary & Rao, 1981), and reduction of the total number of EGF receptors (Cruise et al, 1986). In the light of the increased number of EGF receptors on malignant squamous cells the aforementioned effect might be very promising (Cowley et al, 1986)
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