Curcumin Protects against UVB-Induced Skin Cancers in SKH-1 Hairless Mouse: Analysis of Early Molecular Markers in Carcinogenesis

Abstract

Curcumin (CUR) has been shown to possess a preventive effect against various cancers and interfere with multiple-cell signaling pathways. We evaluated the protective effects of CUR in regression of UVB-induced skin tumor formation in SKH-1 hairless mice and its underlying early molecular biomarkers associated with carcinogenesis. Mice irradiated with UVB at 180 mJ/cm2 twice per week elicited 100% tumor incidence at 20 weeks. Topical application of CUR prior to UVB irradiation caused delay in tumor appearance, multiplicity, and size. Topical application of CUR prior to and immediately after a single UVB irradiation (180 mJ/cm2) resulted in a significant decrease in UVB-induced thymine dimer-positive cells, expression of proliferative cell nuclear antigen (PCNA), terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling, and apoptotic sunburn cells together with an increase in p53 and p21/Cip1-positive cell population in epidermis. Simultaneously, CUR also significantly inhibited NF-κB, cyclooxygenase-2 (COX-2), prostaglandin E2 (PGE2), and nitric oxide (NO) levels. The results suggest that the protective effect of CUR against photocarcinogenesis is accompanied by downregulation of cell proliferative controls, involving thymine dimer, PCNA, apoptosis, transcription factors NF-κB, and of inflammatory responses involving COX-2, PGE2, and NO, while upregulation of p53 and p21/Cip1 to prevent DNA damage and facilitate DNA repair.

Protective Effect of Curcumin Against Acute Ultraviolet B Irradiation‐induced Photo‐damage

“…Tsai et al . get the similar observation in mice treated with topical curcumin and exposed to UVB irradiation only twice weekly over a 20‐week period. However, contact dermatitis caused by treated with curcumin for several weeks have been reported in human .…”

Germinated brown rice and its bioactives modulate the activity of uterine cells in oophorectomised rats as evidenced by gross cytohistological and immunohistochemical changes

“…Histologically, rat uteri treated with GBR and its bioactives showed increased activity of the uterine cells and also the glands. PCNA, which is an indicator of DNA synthesis as well as cell proliferation, showed positive reactions on the treated cells and this showed that the cells are on their early propagation and duplication at the synthetic (S) phase cycle as reported by other workers [38,39]. Thus, the cells of the treated groups were in the early stages of duplication and showed strongly positive nuclear reactivity.…”

Use of Polyphenolic Compounds in Dermatologic Oncology

“…In an animal study, curcumin (10 mmol/200 mL acetone) was topically applied 30 minutes prior to UVB (180 mJ/cm 2 ) irradiation [54]: curcumin decreased UVB-induced thymine dimer-positive cells, expression of proliferation cell nuclear antigen (PCNA), terminal deoxynucleotidyl transferase-mediated 2′-deoxyuridine 5′-triphosphate (dUTP) nick end labeling, apoptotic sunburn cells, and increased protein p53 (p53) and cyclin-dependent kinase inhibitor 1A (Cip/p21)-positive cells. Such findings were associated with inhibition of prostaglandin E2 (PGE-2) and nitric oxide (NO) [54], as well as the cyclooxygenase-2 (COX-2) expression through nuclear factor-kappa B (NF-κB) [54, 55].…”

“…Such findings were associated with inhibition of prostaglandin E2 (PGE-2) and nitric oxide (NO) [54], as well as the cyclooxygenase-2 (COX-2) expression through nuclear factor-kappa B (NF-κB) [54, 55]. By blocking NF-κB, curcumin inhibits T-cell response, and both epidermal and fibroblast proliferation [50] (Table 1).…”