%0 Journal Article
%T Shikonin enhances efficacy of a gene-based cancer vaccine via induction of RANTES
%A Hui-Ming Chen
%A Pi-Hsueh Wang
%A Kandan Aravindaram
%A Yun-Hsiang Chen
%A Hsiu-Hui Yu
%A Wen-Chin Yang
%A Ning-Sun Yang
%J Journal of Biomedical Science
%D 2012
%I BioMed Central
%R 10.1186/1423-0127-19-42
%X The mRNA and protein expression of RANTES were detected by RT-PCR and ELISA, respectively. The regional expression of RANTES and tissue damage in test skin were evaluated via immunohistochemistry assay. Fluorescein isothiocyanate sensitization assay was performed to trace the trafficking of DCs from the skin vaccination site to draining lymph nodes. Adjuvantic effect of shikonin on gene gun-delivered human gp100 (hgp100) DNA cancer vaccine was studied in a human gp100-transfected B16 (B16/hgp100) tumor model.Among various phytochemicals tested, shikonin induced the highest level of expression of RANTES in normal skin tissues. In comparison, mouse RANTES cDNA gene transfection induced a higher level of mRANTES expression for a longer period, but caused more extensive skin damage. Topical application of shikonin onto the immunization site before gene gun-mediated vaccination augmented the population of skin DCs migrating into the draining lymph nodes. A hgp100 cDNA gene vaccination regimen with shikonin pretreatment as an adjuvant in a B16/hgp100 tumor model increased cytotoxic T lymphocyte activities in splenocytes and lymph node cells on target tumor cells.Together, our findings suggest that shikonin can effectively enhance anti-tumor potency of a gene-based cancer vaccine via the induction of RANTES expression at the skin immunization site.Shikonin, a phytochemical from the traditional herbal medicine Lithospermum erythrorhizon, has been shown to possess diverse pharmacological properties, including anti-oxidant [1], wound healing [2-4], anti-inflammatory [5] and anti-tumor properties [6,7]. Anti-inflammatory activities of shikonin can be mediated by suppression of TNF-¦Á promoter activity [8] or by regulation of TNF-¦Á pre-mRNA splicing [9]. Wound-healing activity of shikonin resulted in proliferation of fibroblasts and collagen fiber levels in granuloma tissues, and an increase in the CD11b+ cell population in granulation tissues [3,4]. These findings suggest that
%U http://www.jbiomedsci.com/content/19/1/42