Modulation of placental alkaline phosphatase activity and cytokeratins in human HN-1 cells by butyrate, retinoic acid, catecholamines and histamine

Abstract

Summary 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 f,-adrenergic antagonist propranolol partly inhibited the aforementioned enhancement of PLAP activity, whereas the x-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) As is shown in numerous reports, butyrate, retinoic acid, interferon, glucocorticoids, polar solvents, and certain chemotherapeutic agents can modulate terminal differentiation (Augeron & Laboisse, 1984;Burke, 1986;Jetten, 1984;Reiss et al., 1985;Sartorelli, 1985), accompanied by inhibition of proliferation (Pierce & Wallace, 1971;Prasad & Sinha, 1976), morphological changes (Abe & Kufe, 1984;Kamech et al., 1986), and an increase in the production of specific antigens and enzymes (Reese & Politano, 1981;Morita et al., 1982;Abe & Kufe, 1984;Reese et al., 1985), such as CEA and alkaline phosphatase. These effects were in most cases reversible, although some authors claimed a more permanently affected cell progeny after treatment (Augeron & Laboisse, 1984;Reiss et al., 1985). It was indicated that for example butyrate and retinoic acid provided a trigger mechanism, which if properly administered to a cell would eventually lead to a terminally matured tumour cell.Recently 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).The present study, using HN-1 squamous carcinoma cells, demonstrated that butyrate inhibited clonogenicity in soft agar, enhanced placental alkaline phosphatase (PLAP) activity, and increased relative cytokeratin content, in contrast to retinoic acid. Retinoic acid, however, inhibited the enhancement of PL...

Effects of β‐all‐trans retinoic acid on growth, proliferation, and cell death in a multicellular tumor spheroid model for squamous carcinomas

“…This growth inhibition was not just a cytotoxic effect, since MTS regrowth occurred when MTSs were rinsed free of RA and further cultured in RA-free medium (Sacks et al, 198913). Inhibition of MTS growth by RA agrees with reports of decreased proliferation by colony-forming efficiency for some SCC cell lines (Cline and Rice, 1983;Lotan et al, 1987;Sarkar and Das, 19881, while in other SCC cell lines proliferation is unaffected or even stimulated (Reiss et al, 1985;Lotan et al, 1987;Bijman et al, 1987).…”

In Vitro Phenotypic Alteration of Human Melanoma Cells Induced by Differentiating Agents: Heterogeneous Effects on Cellular Growth and Morphology, Enzymatic Activity, and Antigenic Expression

“…Thus ALP is not associated with melanogenesis and is not a general marker for differentiation in pigment cells. Endogenous ALP activity is extremely low in frozen tissues of normal melanocytes and benign melanocytic lesions (unpublished data), in the epidermis generally (Mier and van Rennes, 1982), and in melanomas (Nordenberg et al, 1987) and other tumors (Kim et al, 1980;Bijman et al, 1987). Therefore, the induction of ALP activity appears to occur randomly rather than as an intrinsic feature of differentiated phenotypes.…”

Repurposing Drugs in Oncology (ReDO)—Propranolol as an anti-cancer agent

“…The converse, a reduction of proliferation due to PRO was also reported in the same era, for example Iwata, Kariya and Fujimoto showed that in a ciliated protozoan beta-adrenergic blockade, with PRO and other agents, was associated with a reduced rate of growth [97]. It has since been shown that PRO is able to inhibit the increase in cancer cell proliferation associated with catecholamines or isoproterenol in a number of cancer cell types [56, 98–100]. …”