Email updates

Keep up to date with the latest news and content from Journal of Biomedical Science and BioMed Central.

Journal App

google play app store

MST logoThe cost of publication in Journal of Biomedical Science is borne by the Ministry of Science and Technology, Taiwan.

Open Access Highly Accessed Research

Shikonin enhances efficacy of a gene-based cancer vaccine via induction of RANTES

Hui-Ming Chen12, Pi-Hsueh Wang2, Kandan Aravindaram2, Yun-Hsiang Chen2, Hsiu-Hui Yu2, Wen-Chin Yang2 and Ning-Sun Yang23456*

Author Affiliations

1 Department and Institute of Pharmacology, National Yang-Ming University, Taipei, Taiwan

2 Institute of Agricultural Biotechnology Research Center, Academia Sinica, Taipei, Taiwan

3 Institute of Biotechnology, National Taiwan University, Taipei, Taiwan

4 Department of Life Sciences, National Central University, Taipei, Taiwan

5 Graduate institute of biotechnology, National Chung Hsing University, Taichung, Taiwan

6 Institute of Agricultural Biotechnology Research Center, Academia Sinica, No. 128, Academia Sinica Rd. Sec. 2, Nankang District, Taipei 11529, Taiwan

For all author emails, please log on.

Journal of Biomedical Science 2012, 19:42  doi:10.1186/1423-0127-19-42

Published: 12 April 2012

Abstract

Background

Shikonin, a phytochemical purified from Lithospermum erythrorhizon, has been shown to confer diverse pharmacological activities, including accelerating granuloma formation, wound healing, anti-inflammation and others, and is explored for immune-modifier activities for vaccination in this study. Transdermal gene-based vaccine is an attractive approach for delivery of DNA transgenes encoding specific tumor antigens to host skin tissues. Skin dendritic cells (DCs), a potent antigen-presenting cell type, is known to play a critical role in transmitting and orchestrating tumor antigen-specific immunities against cancers. The present study hence employs these various components for experimentation.

Method

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.

Results

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.

Conclusion

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.