Differential Effects of Retinoids on DNA Synthesis in Calcium-Regulated Murine Epidermal Keratinocyte Cultures

Tong, Philip; Mayes, Douglas M.; Wheeler, Larry A.

doi:10.1111/1523-1747.ep12462107

Cited by 23 publications

(11 citation statements)

References 26 publications

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“…These observations are in line with inhibition of cell proliferation observed in HaCaT keratinocytes, other human keratinocyte cell lines, and various human cancers following treatment with retinoic acid [49-53]. Retinoic acid also inhibits proliferation of mouse primary keratinocytes, which is consistent with previous studies [54] and with inhibition of skin cancer by retinoids observed in several mouse models [55-61]. Combined, these observations are highly inconsistent with the proposed pathway suggesting that activating PPARβ/δ by retinoic acid will enhance cell growth of human keratinocytes [43, 47].…”

Section: Regulation Of Cell Proliferation In Skin and Keratinocytesupporting

confidence: 91%

Sorting out the functional role(s) of peroxisome proliferator-activated receptor-β/δ (PPARβ/δ) in cell proliferation and cancer

Peters

Gonzalez

2009

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer

154

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Peroxisome proliferator-activated receptor-β/δ (PPARβ/δ) has many beneficial physiological functions ranging from enhancing fatty acid catabolism, improving insulin sensitivity, inhibiting inflammation and increasing oxidative myofibers allowing for improved athletic performance. Thus, given the potential for targeting PPARβ/δ for the prevention and/or treatment of diseases including diabetes, dyslipidemias, metabolic syndrome and cancer, it is critical to clarify the functional role of PPARβ/δ in cell proliferation and associated disorders such as cancer. However, there is considerable controversy whether PPARβ/δ stimulates or inhibits cell proliferation. This review summarizes the literature describing the influence of PPARβ/δ on cell proliferation, with an emphasis toward dissecting the data that give rise to opposing hypotheses. Suggestions are offered to standardize measurements associated with these studies so that interlaboratory comparisons can be accurately assessed.

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Section: Regulation Of Cell Proliferation In Skin and Keratinocytesupporting

confidence: 91%

Sorting out the functional role(s) of peroxisome proliferator-activated receptor-β/δ (PPARβ/δ) in cell proliferation and cancer

Peters

Gonzalez

2009

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer

154

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“…Stimulation by high calcium concentration may be mediated by increased concentrations of IGFs I and II. Proliferation of mouse epidermal cells is increased in media with 2% serum and inhibited in media with 10% serum by 3 mM calcium (Tong et al 1988). The addition of plateled-derived growth factor and epidermal growth factor reduces the calcium requirement for human fibroblast proliferation (Belsholtz and Westermark 1984).…”

Section: Discussionmentioning

confidence: 99%

Effects of extracellular calcium on the proliferation and differentiation of porcine osteoblasts in vitro

Eklou-Kalonji

Denis

Lieberherr

et al. 1998

Cell and Tissue Research

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We examined the effects of various extracellular calcium concentrations on DNA content, procollagen type I carboxy-terminal propeptide (PICP) release (reflects type I collagen synthesis), and alkaline phosphatase activity of porcine osteoblasts. Osteoblasts seeded in control medium (2.2 mM calcium) were transferred to low (0. 5 or 1 mM) calcium medium or to high (3, 5, 7, or 10 mM) calcium medium at different stages of the culture period and for different incubation times. When osteoblasts were transferred to low or high (3 or 5 mM) calcium medium 1 or 2 days after plating and kept in that medium until the end of the culture period, PICP release was inhibited, but DNA content and alkaline phosphatase activity were unchanged, except in 5 mM calcium, which inhibited alkaline phosphatase activity. Short-term culture of subconfluent and near-confluent osteoblasts in 7 or 10 mM calcium for 48 h inhibited DNA content. DNA content returned to normal levels when cells were transferred back to control medium, whereas alkaline phosphatase inhibition induced by 5, 7, or 10 mM calcium was not reversible. Short-term culture in high calcium media did not affect PICP release. Thus, in porcine osteoblasts, low and high extracellular calcium concentrations affect DNA content, PICP release, and the expression of osteoblastic phenotype markers (alkaline phosphatase activity). These effects are dependent on the duration of calcium treatment and the state of differentiation of the osteoblasts.

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“…With both populations, all-trans-retinoic acid was able to stimulate the proliferation of growth-arrested cells [14][15][16], Prior stud ies had shown that, depending on the cell type, their age, the conditions of mainte nance, and the proliferation status at the time of treatment, various retinoids could either stimulate or inhibit cell growth [9][10][11][12][13]. Our studies were the first to show consistent stimulation of both human skin fibroblasts and epithelial cells and to define some of the conditions required for stimulation.…”

Section: Discussionmentioning

confidence: 99%

“…In contrast, oral administration of etretinate to subjects with psoriasis suppresses hyper proliferation of psoriatic kératinocytes [7,8]. These apparently paradoxical effects of reti noids are also observed in vitro, where reti noids can either stimulate or inhibit fibro blast and epithelial cell proliferation, de pending on the source of the cells and the conditions of maintenance [9][10][11][12][13].…”

Section: Introductionmentioning

confidence: 99%

A Direct Comparison of Pharmacologic Effects of Retinoids on Skin Cells in vitro and in vivo

Varani

Gendimenico

Shah

et al. 1991

Skin Pharmacol Physiol

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The purpose of these studies was to directly compare the pharmacologic effects of retinoids on cutaneous cells in vitro and in vivo. Previously, it was demonstrated that all-trans-retinoic acid stimulates the proliferation of growth-arrested human keratinocytes and fíbroblasts in culture. In the present studies, all-trans-retinoic acid was compared to three other retinoids – 13-cis-retinoic acid, P-[(E)-2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-napthalenyl-l-propenyl] benzoic acid (TTNPB) and M-[(E)-2-(5,6,7,8-tetrahydro-5,5,8,8,-tetramethyl-2-napthalenyl-l-propenyl] benzoic acid (meta-carboxy-TTNPB] – for growth stimulation using a cultured human squamous epithelial cell line (UM-SCC-1) and human dermal fíbroblasts. These four retinoids were also evaluated for their effects on reduction of horn-filled utriculi when topically applied to the skin of rhino mice. All-trans-retinoic acid stimulated proliferation of both fíbroblasts and epithelial cells over concentrations ranging from 0.01 to 1.0 μg/ml. In fíbroblasts, 13-cis-retinoic acid was less potent than all-trans-retinoic acid, whereas, in epithelial cells these two retinoids were equipotent. In contrast, TTNPB was more potent than all-trans-retinoic acid at stimulating the growth of both fíbroblasts and epithelial cells. The analog, meta-carboxy-TTNPB was essentially inactive as a growth stimulator of both cell types. In the rhino mouse utriculus reduction model, the rank order of potency for the retinoids was the same as that for in vitro cell growth stimulation (TTNPB > all-trans-retinoic acid > 13-cis-retinoic acid). Meta-carboxy-TTNPB was inactive at reducing utriculi at a dose of 5,000 times the ED₅₀ of TTNPB. In summary, the results of these studies show that the effects of retinoids on stimulating proliferation of fíbroblasts and epithelial cells correlate with their effects at reducing utriculi in the rhino mouse. Therefore, these in vitro models appear to have good relevance for studying the mechanisms of the pharmacologic effects of retinoids in vivo.

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Differential Effects of Retinoids on DNA Synthesis in Calcium-Regulated Murine Epidermal Keratinocyte Cultures

Cited by 23 publications

References 26 publications

Sorting out the functional role(s) of peroxisome proliferator-activated receptor-β/δ (PPARβ/δ) in cell proliferation and cancer

Sorting out the functional role(s) of peroxisome proliferator-activated receptor-β/δ (PPARβ/δ) in cell proliferation and cancer

Effects of extracellular calcium on the proliferation and differentiation of porcine osteoblasts in vitro

A Direct Comparison of Pharmacologic Effects of Retinoids on Skin Cells in vitro and in vivo

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