Shikonin induces immunogenic cell death in tumor cells and enhances dendritic cell-based cancer vaccine |
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Authors: | Hui-Ming Chen Pi-Hsueh Wang Swey-Shen Chen Chih-Chun Wen Yun-Hsiang Chen Wen-Chin Yang Ning-Sun Yang |
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Institution: | 1. Department and Institute of Pharmacology, National Yang-Ming University, Taipei, Taiwan, ROC 2. Institute of Agricultural Biotechnology Research Center, Academia Sinica, No. 128, Academia Sinica Rd. Sec. 2, Nankang District, Taipei, 11529, Taiwan, ROC 5. Department of Allergy and Vaccinology, IGE Therapeutics, Inc., San Diego, CA, 92131, USA 6. Department of Molecular Biology, The Scripps Research Institute, San Diego, CA, 92037, USA 3. Institute of Biotechnology, National Taiwan University, Taipei, Taiwan, ROC 4. Department of Life Sciences, National Central University, Zhongli, Taiwan, ROC 7. Graduate Institute of Biotechnology, National Chung Hsing University, Taichung, Taiwan, ROC
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Abstract: | Immunogenic cell death is characterized by damage-associated molecular patterns, which can enhance the maturation and antigen uptake of dendritic cells. Shikonin, an anti-inflammatory and antitumor phytochemical, was exploited here as an adjuvant for dendritic cell-based cancer vaccines via induction of immunogenic cell death. Shikonin can effectively activate both receptor- and mitochondria-mediated apoptosis and increase the expression of all five tested damage-associated molecular patterns in the resultant tumor cell lysates. The combination treatment with damage-associated molecular patterns and LPS activates dendritic cells to a high maturation status and enhances the priming of Th1/Th17 effector cells. Shikonin-tumor cell lysate-loaded mature dendritic cells exhibit a high level of CD86 and MHC class II and activate Th1 cells. The shikonin-tumor cell lysate-loaded dendritic cell vaccines result in a strong induction of cytotoxic activity of splenocytes against target tumor cells, a retardation in tumor growth, and an increase in the survival of test mice. The much enhanced immunogenicity and efficacy of the current cancer vaccine formulation, that is, the use of shikonin-treated tumor cells as cell lysates for the pulse of dendritic cells in culture, may suggest a new ex vivo approach for developing individualized, dendritic cells-based anticancer vaccines. |
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