The present study revealed the effects of
Lycopene enriched tomato extract (LycT) on chemically induced
skin cancer in mice. Skin
tumors were induced by topical application of
7,12-Dimethylbenz(a)anthracene (DMBA) [500 nmol/100 ul of
acetone, twice a week for two weeks] and 12-O-tetradecanoyl phorbol-13-acetate (TPA) [1.7 nmol/100 ul of
acetone, twice a week for eighteen weeks] and LycT (5 mg/kg b.w.) was administered orally. Male Balb/c mice were divided into four groups (n = 15 per group): control, DMBA/TPA, LycT and LycT + DMBA/TPA. The chemopreventive response of LycT to skin
tumorigenesis was evident by inhibition in
tumor incidence, number, size, burden and volume in LycT + DMBA/TPA group when compared to DMBA/TPA group. This was associated with inhibition of cell proliferation in LycT + DMBA/TPA group as observed by the decrease in epidermal morphometric parameters and
mRNA and
protein expression of
proliferating cell nuclear antigen when compared to DMBA/TPA group (p ≤ 0.05). LycT decreased (p ≤ 0.05) the
mRNA and
protein expression of angiogenic genes (
vascular endothelial growth factor,
angiopoietin-2,
basic fibroblast growth factor) in LycT + DMBA/TPA group, suggesting its anti-angiogenic effects. The increase (p ≤ 0.05) in
protein expression of connexin-32 and 43 in LycT + DMBA/TPA group suggests improved inter cellular communication when compared to DMBA/TPA group. Histochemical studies demonstrated that the components of extracellular matrix (
fibrous proteins and
mucopolysaccharides) were also modulated during skin
carcinogenesis and its
chemoprevention by LycT. The decrease in cell proliferation parameters and expression of angiogenesis associated genes, modulation of ECM components and increase in expression of
connexins suggest that LycT improved multiple dysregulated processes during
chemoprevention of
skin cancer.