Dietary Lycopene Protects SKH-1 Mice Against Ultraviolet B-Induced Photocarcinogenesis

December 2019 | Volume 18 | Issue 12 | Original Article | 1244 | Copyright © December 2019

Karen E. Burke MD PhD,a Xueyan Zhou MD MS,a,b Yongyin Wang PhD,a,c and Huachen Wei MD PhDa

aDepartment of Dermatology, Icahn School of Medicine at Mount Sinai, New York, NY
bDepartment of Internal Medicine, Gerontology and Geriatric Medicine,Wake Forest University School of Medicine, Winston-Salem, NC
cMedtronic Diabetes MiniMed, Northridge, CA
dDepartment of Dermatology, No.1 Hospital, China Medical University, Shengyang, China

Abstract
Lycopene, an acyclic hydrocarbon, non-provitamin A carotenoid, is a potent antioxidant with well-documented anticancer properties. In this study, we investigated the effects of dietary lycopene on sub-acute and chronic ultraviolet B (UVB)-induced skin carcinogenesis in SKH-1 mice. Groups of three mice were fed with a nonsupplemented or 1% lycopene diet for two weeks before and throughout two weeks of UVB irradiation (30 mJ/cm2 UVB, thrice weekly). The lycopene diet significantly reduced the formation of pyrimidine dimers (PDs) and the expression of proliferative cellular nuclear antigen (PCNA) in UVB-irradiated skin. Then groups of eighteen mice were each fed with control diet or with a 0.25% or 1% (w/w) lycopene-supplemented diet for 40 weeks, beginning one week before UVB irradiation (30 mJ/cm2 UVB, thrice weekly for 23 weeks) and continuing after termination of UVB. Lycopene significantly inhibited the onset and decreased the incidence, multiplicity, and tumor weights of UVB-induced skin tumors. UVB-induced epidermal hyperplasia and PCNA expression were still remarkably inhibited by dietary lycopene, even up to 40 weeks. No significant difference in protection was detected between the low and high concentrations of lycopene. These results demonstrate that dietary lycopene does protect against UVB-induced epidermal hyperplasia and carcinogenesis.
J Drugs Dermatol. 2019;18(12):1244-1254.

INTRODUCTION

By far, the most common human malignancy is skin cancer. The incidence is increasing at an astonishing rate, with more than 5.4 million new cases of non-melanoma skin cancer (NMSC) diagnosed each year in the United States1 that is 925 new skin cancers diagnosed each hour awake! The most common causative factor is excessive exposure to sunlight, which cannot be avoided with our daily occupational and recreational activities. The rapid rise is enhanced not only by increased travel with vacations in sunny environments, but also by an increase in high risk groups, such as immunocompromised organ transplant patients.2-4 The most directly carcinogenic spectrum of sunlight is ultraviolet B (UVB) radiation,5 both a tumor initiator and promoter.6-8 Generation of reactive oxygen species (ROS) by UVB exposure not only induces oxidative DNA damage, leading to not only tumor initiation,9 but also to activation of many growth factors and signal transduction cascades including those involved in tumor promotion, such as tyrosine protein kinase (TPK) and mitogen activating protein (MAP) kinase pathways.10-12 UVB-induced inflammation and immunosuppression further contribute to photocarcinogenesis.11 Therefore, topical or systemic supplementation by antioxidants may protect skin against UVB-induced photodamage and carcinogenesis.13 With current emphasis on preventative medicine and healthy eating, recent research for new anticancer drugs focuses more on natural nutrients from the regular human diet. These compounds rarely cause adverse side effects, and they act on a wide range of molecular targets involved in carcinogenesis. Lycopene is a carotenoid found in tomatoes and other red-colored fruits and vegetables.14 This powerful dietary antioxidant has received considerable attention in recent years. A potent scavenger of oxygen radicals, lycopene has the highest singlet oxygen quenching ability when compared to 31 other antioxidants.15-17 Numerous epidemiological, in vitro and animal studies provide convincing evidence that lycopene prevents a variety of cancers,18 including prostate,19-21 breast,22-24 cervical,25 gastric,26 colon,27 lung,28,29 liver,30,31 bladder,32 and renal cell cancers.33 Only recently have studies assessed whether lycopene has potential for prevention of skin cancer.34,35 Although the anticarcinogenic effects of lycopene are thought to be primarily due to its antioxidant properties,36 other mechanisms have also been demonstrated, such as enhancing the gap junctional communication (GJC),37 suppressing the growth factor receptor signaling,38,39 inducing the apoptosis of cancerous cells,34,40 regulating the cell cycle.38,41 and stimulating the immune system.42