Online citations, reference lists, and bibliographies.
← Back to Search

Chemoprevention Of Human Actinic Keratoses By Topical Dl-α-tocopherol

J. Foote, J. Ranger-Moore, J. Einspahr, K. Saboda, J. Kenyon, J. Warneke, R. Miller, R. Goldman, Min-jian Xu, D. Roe, D. Alberts
Published 2009 · Medicine

Save to my Library
Download PDF
Analyze on Scholarcy
Share
Prior research shows that topical application of free, nonfatty acid–conjugated vitamin E (dl-α-tocopherol) prevents skin cancer in mice, as well as immunosuppression induced by UVB radiation. This study investigated the chemopreventive potential of dl-α-tocopherol in humans through monitoring surrogate end point biomarkers in sun-damaged skin. Contralateral arms of healthy human volunteers with actinic keratoses (AK) were randomly assigned to receive either 12.5% dl-α-tocopherol or placebo in a crème base for 6 months. Changes in number of AKs, levels of p53 protein expression, proliferating cell nuclear antigen, and polyamines were assessed along with skin and systemic vitamin E levels. Following treatment, plasma concentration levels of dl-α-tocopherol were unchanged, but skin levels were highly elevated (P < 0.001). Levels of p53 and proliferating cell nuclear antigen did not change significantly, whereas number of AKs declined insignificantly in both placebo and treatment arms. Regression models showed significant decreases in putrescine, spermidine, spermine, and total polyamine concentrations following treatment. Topically applied dl-α-tocopherol was substantially absorbed in skin, but the 6-month application did not significantly reduce numbers of preexisting AKs on moderately to severely sun-damaged forearms. Increases in polyamine synthesis are expected during tumor initiation and promotion; conversely, the significant reductions in polyamine levels resulting from the topical dl-α-tocopherol application are consistent with reductions in tumorigenesis potential. Topical tocopherol did not normalize established sun-induced lesions, but dl-α-tocopherol–induced reductions in polyamine metabolism are consistent with the inhibition of skin squamous cell carcinogenesis as seen in previous human trials and animal models.
This paper references
Incorporated (1989-1996 Copyright). SAS Statistical Software System version 9
Evaluation of proliferating cell nuclear antigen as a surrogate end point biomarker in actinic keratosis and adjacent, normal-appearing, and non-sun-exposed human skin samples.
J. Einspahr (1996)
Oxidative targets in the stratum corneum. A new basis for antioxidative strategies.
J. Thiele (2001)
10.1038/jid.2008.159
Recent trends in incidence of cutaneous melanoma among US Caucasian young adults.
M. Purdue (2008)
10.1056/NEJM199310143291602
Reduction of solar keratoses by regular sunscreen use.
S. C. Thompson (1993)
10.1016/S0891-5849(96)00339-5
The importance of L-arginine metabolism in melanoma: an hypothesis for the role of nitric oxide and polyamines in tumor angiogenesis.
M. Joshi (1997)
10.1016/0006-2944(79)90069-3
Effects of ultraviolet light on epidermal polyamine metabolism.
N. Seiler (1979)
Ornithine decarboxylase overexpression is a sufficient condition for tumor promotion in mouse skin.
T. O'brien (1997)
10.1016/S0304-3835(97)04663-6
Retinoids in prevention of skin cancer.
T. Moon (1997)
10.1067/MJD.2000.103342
Epidemiology of actinic keratoses and squamous cell carcinoma.
S. Salasche (2000)
10.1001/ARCHDERM.1997.03890460087010
The molecular basis of nonmelanoma skin cancer: new understanding.
D. Grossman (1997)
10.1001/JAMA.294.6.681
Incidence of basal cell and squamous cell carcinomas in a population younger than 40 years.
L. Christenson (2005)
Expression of p53 protein in actinic keratosis, adjacent, normal-appearing, and non-sun-exposed human skin.
J. Einspahr (1997)
10.1016/S0140-6736(88)91658-3
MALIGNANT TRANSFORMATION OF SOLAR KERATOSES TO SQUAMOUS CELL CARCINOMA
R. Marks (1988)
10.1111/j.1600-0560.1992.tb01598.x
Proliferating cell nuclear antigen (PCNA) in common epidermal lesions.
W. A. Geary (1992)
10.1093/CARCIN/18.6.1195
Involvement of polyamines in selenomethionine induced apoptosis and mitotic alterations in human tumor cells.
C. Redman (1997)
Distribution patterns and frequency of proliferating cells in cutaneous keratinocytic neoplasms
T Saida (1992)
10.1080/01635589109514117
Topical vitamin E inhibition of immunosuppression and tumorigenesis induced by ultraviolet irradiation.
H. Gensler (1991)
10.1016/0024-3205(73)90111-2
The roles of the polyamines, putrescine, spermidine, and spermine in normal and malignant tissues.
D. H. Russell (1973)
10.1016/0190-9622(92)70104-N
Distribution patterns and frequency of proliferating cells in cutaneous keratinocytic neoplasms. Immunohistochemical study with a monoclonal antibody (TOB7) used against proliferating cell nuclear antigen.
T. Saida (1992)
PCNA expression in cutaneous keratinous neoplasms and verruca vulgaris.
N. Penneys (1992)
10.1016/S0190-9622(98)70196-3
Clinical and histologic trends of melanoma.
T. Johnson (1998)
Effect of retinol in preventing squamous cell skin cancer in moderate-risk subjects: a randomized, double-blind, controlled trial. Southwest Skin Cancer Prevention Study Group.
T. Moon (1997)
10.1159/000056395
Oxidative Targets in the Stratum corneum
J. Thiele (2001)
10.1046/J.0022-202X.2001.01469.X
Aging- and photoaging-dependent changes of enzymic and nonenzymic antioxidants in the epidermis and dermis of human skin in vivo.
G. Rhie (2001)
10.1016/S0021-9673(01)93283-2
High-performance liquid chromatographic method for the determination of dansyl-polyammines
S. Minocha (1990)
10.1038/SJ.NEO.7900061
Relationship of p53 mutations to epidermal cell proliferation and apoptosis in human UV-induced skin carcinogenesis.
J. Einspahr (1999)
Southwest Skin Cancer Prevention Study Group. Effect of retinol in preventing squamous cell skin cancer in moderate-risk subjects: a randomized, doubleblind, controlled trial
TE Moon (1997)
Chemoprevention of human actinic keratoses by topical 2-(difluoromethyl)-dl-ornithine.
D. Alberts (2000)
Modulation of biologic endpoints by topical difluoromethylornithine (DFMO), in subjects at high-risk for nonmelanoma skin cancer.
J. Einspahr (2002)
Polyamines regulate expression of the neoplastic phenotype in mouse skin.
A. Peralta Soler (1998)
10.1080/01635589609514475
Disposition and metabolism of topically administered alpha-tocopherol acetate: a common ingredient of commercially available sunscreens and cosmetics.
D. Alberts (1996)
10.1016/0300-9084(88)90028-4
Photoprotective effect of vitamins A and E on polyamine and oxygenated free radical metabolism in hairless mouse epidermis.
N. Khettab (1988)
A Guide to the Polyamines
S. Cohen (1998)
A nonsaponification method for the determination of carotenoids, retinoids, and tocopherols in solid human tissues.
Y. M. Peng (1993)
High-performance liquid chromatographic method for the determination of dansyl-polyamines ”
S. Minocha (2000)
10.1080/01635589609514474
Importance of the form of topical vitamin E for prevention of photocarcinogenesis.
H. Gensler (1996)
10.1016/0304-3835(94)90234-8
Analysis of the p53 gene in human precancerous actinic keratosis lesions and squamous cell cancers.
M. Nelson (1994)



This paper is referenced by
10.1080/01635581.2013.785005
Protective Effect of Topical Application of α-Tocopherol and/or N-Acetyl Cysteine on Argemone Oil/Alkaloid-Induced Skin Tumorigenesis in Mice
Anu Pal (2013)
10.22037/IJPR.2013.1268
An Investigation into Some Effective Factors on Encapsulation Efficiency of Alpha-Tocopherol in MLVs and the Release Profile from the Corresponding Liposomal Gel
H. Tabandeh (2013)
10.1002/14651858.CD004415.pub2
Interventions for actinic keratoses.
A. Gupta (2012)
10.1201/B15642-3
Nanotechnology Applications in Dermatology
David Schairer (2013)
10.1684/ejd.2013.1923
Therapeutic strategies for actinic keratoses--a systematic review.
D. Nashan (2013)
10.1016/j.drudis.2018.11.020
Essential oils: from prevention to treatment of skin cancer.
P. Pavithra (2019)
Systematic review of the natural course of actinic keratosis and their relation to squamous cell carcinoma
R. Werner (2014)
10.1111/bjd.12420
The natural history of actinic keratosis: a systematic review
R. Werner (2013)
10.1016/B978-1-4377-1788-4.00043-5
Topical Treatment of Skin Cancer
V. Williams (2011)
10.1007/s40257-016-0208-2
Chemoprevention of Keratinocyte Carcinomas: An Updated Review
J. Mounessa (2016)
10.1016/j.canlet.2014.11.001
Skin cancer and new treatment perspectives: a review.
M. F. Simões (2015)
10.4137/CGM.S21219
Skin Carcinogenesis Studies Using Mouse Models with Altered Polyamines
Shannon L Nowotarski (2015)
10.1111/jdv.13179
Methods and Results Report – Evidence and consensus‐based (S3) Guidelines for the Treatment of Actinic Keratosis –International League of Dermatological Societies in cooperation with the European Dermatology Forum
R. Werner (2015)
Nonsurgical innovations in the treatment of nonmelanoma skin cancer.
S. Amini (2010)
10.1002/14651858.CD012266
Interventions for preventing keratinocyte cancer in high-risk groups not receiving immunosuppressive therapy
M. A. Morales-Sánchez (2016)
Semantic Scholar Logo Some data provided by SemanticScholar