Stimulatory Effect of Topical Application of Caffeine on UVB-Induced Apoptosis in the Epidermis of p53 and Bax Knockout Mice

Lu, Yao-Ping; Lou, You-Rong; Peng, Qingyun; Xie, Jun; Conney, Allan H.

doi:10.1158/0008-5472.can-04-0760

Cited by 73 publications

(96 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The percentage of apoptotic cells at the UVB dose used in the mouse experiments (1,250 J/m 2 , a minimal erythemal dose that induces a barely perceptible sunburn) was Ϸ1.5% in wild-type mice after 1 day of exposure (D. Knezevic and D.E.B., unpublished work; see also ref. 41). If an epidermal cell that is undergoing apoptosis is visible for 4 h (33-35), then the apoptosis rate is 0.02/4 h ϭ 0.12 day Ϫ1 , which agrees with the model's estimate of 0.11 day Ϫ1 .…”

Section: Discussionsupporting

confidence: 81%

Preneoplastic lesion growth driven by the death of adjacent normal stem cells

Chao

Eck

Brash

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Clonal expansion of premalignant lesions is an important step in the progression to cancer. This process is commonly considered to be a consequence of sustaining a proliferative mutation. Here, we investigate whether the growth trajectory of clones can be better described by a model in which clone growth does not depend on a proliferative advantage. We developed a simple computer model of clonal expansion in an epithelium in which mutant clones can only colonize space left unoccupied by the death of adjacent normal stem cells. In this model, competition for space occurs along the frontier between mutant and normal territories, and both the shapes and the growth rates of lesions are governed by the differences between mutant and normal cells' replication or apoptosis rates. The behavior of this model of clonal expansion along a mutant clone's frontier, when apoptosis of both normal and mutant cells is included, matches the growth of UVB-induced p53-mutant clones in mouse dorsal epidermis better than a standard exponential growth model that does not include tissue architecture. The model predicts precancer cell mutation and death rates that agree with biological observations. These results support the hypothesis that clonal expansion of premalignant lesions can be driven by agents, such as ionizing or nonionizing radiation, that cause cell killing but do not directly stimulate cell replication.clonal expansion ͉ computer simulation ͉ skin cancer ͉ TP53 ͉ UVB

show abstract

Section: Discussionsupporting

confidence: 81%

Preneoplastic lesion growth driven by the death of adjacent normal stem cells

Chao

Eck

Brash

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

show abstract

“…The four experimental groups were treated as follows: group 1= normal skin group; group 2=UVB group; group 3=UVB+blank ME4 (UVB+vehicle); group 4=UVB+CAF-loaded ME4 (UVB+ CAF). Immediately after UVB irritation, 120 μl of either blank ME4 and CAF-loaded ME4 (1%, w/w) was applied to the mice dorsal site (about 25 mm length and 5 mm width) in group 3 and group 4, respectively (24,25). After 6 h, the skin specimens were excised, embedded, and stained by hematoxylin and eosin for the observation of apoptotic cells in the epidermis.…”

Section: In Vivo Pharmacodynamics Studiesmentioning

confidence: 99%

A Novel Topical Targeting System of Caffeine Microemulsion for Inhibiting UVB-Induced Skin Tumor: Characterization, Optimization, and Evaluation

Liu

et al. 2015

AAPS PharmSciTech

View full text Add to dashboard Cite

Abstract. The purpose of the present study was to develop an optimal microemulsion (ME) formulation as topical nanocarrier of caffeine (CAF) to enhance CAF skin retention and subsequently improve its therapeutic effect on UVB-induced skin carcinogenesis. The pseudo-ternary phase diagram was developed composing of Labrafil M 1944 CS as oil phase, Cremophor EL as surfactant, tetraglycol as cosurfactant, and water. Four ME formulations at water content of 50, 60, 70, and 80% were prepared along the water dilution line of oil to surfactant ratio of 1:3 and characterized in terms of morphology, droplet size, and electric conductivity. A gel at the same drug loads (1%, w/w) was used as control. Ex vivo skin permeation studies were conducted for ME optimization. The optimized formulation (ME4) was composed of 5% (w/w) Labrafil M 1944 CS, 15% (w/w) Smix (2/1, Cremophor EL and tetraglycol), and 80% (w/w) aqueous phase. The skin location amount of CAF from ME4 was nearly 3-fold higher than control (P<0.05) with improved permeated amount through the skin. The skin targeting localization of hydrophilic substance from ME4 was further visualized through fluorescent-labeled ME by a confocal laser scanning microscope. In pharmacodynamics studies, CAF-loaded ME4 was superior in terms of increasing apoptotic sunburn cells (P<0.05) as compared with control. Overall results suggested that the ME4 might be a promising vehicle for the topical delivery of CAF.

show abstract

“…37 The number of UVB-induced sunburn cells in p53 À/À mice is only B20% of those observed in wild-type mice, indicating a crucial role of p53 in UVBinduced apoptosis. 38 Mice expressing mutant p53 or those deficient in p53 develop normally and epidermal formation is not impaired, suggesting that there is no role for p53 in cornification. However, these mice are more sensitive to induction of squamous cell carcinoma after chronic UVB irradiation.…”

Section: Transcription Factors P53 Familymentioning

confidence: 99%

Death penalty for keratinocytes: apoptosis versus cornification

et al. 2005

View full text Add to dashboard Cite

Homeostasis implies a balance between cell growth and cell death. This balance is essential for the development and maintenance of multicellular organisms. Homeostasis is controlled by several mechanisms including apoptosis, a process by which cells condemned to death are completely eliminated. However, in some cases, total destruction and removal of dead cells is not desirable, as when they fulfil a specific function such as formation of the skin barrier provided by corneocytes, also known as terminally differentiated keratinocytes. In this case, programmed cell death results in accumulation of functional cell corpses. Previously, this process has been associated with apoptotic cell death. In this overview, we discuss differences and similarities in the molecular regulation of epidermal programmed cell death and apoptosis. We conclude that despite earlier confusion, apoptosis and cornification occur through distinct molecular pathways, and that possibly antiapoptotic mechanisms are implicated in the terminal differentiation of keratinocytes.

show abstract

Stimulatory Effect of Topical Application of Caffeine on UVB-Induced Apoptosis in the Epidermis of p53 and Bax Knockout Mice

Cited by 73 publications

References 25 publications

Preneoplastic lesion growth driven by the death of adjacent normal stem cells

Preneoplastic lesion growth driven by the death of adjacent normal stem cells

A Novel Topical Targeting System of Caffeine Microemulsion for Inhibiting UVB-Induced Skin Tumor: Characterization, Optimization, and Evaluation

Death penalty for keratinocytes: apoptosis versus cornification

Contact Info

Product

Resources

About