TCM phytochemical shikonin may be developed to serve as adjuvant for cancer vaccines
A research team led by Dr. Ning-Sun Yang, a former Distinguished Research Fellow (now a distinguished visiting chair) at the Agricultural Biotechnology Research Center, has recently used herbal medicine-derived shikonin (SHK) in a tumor-coculturing, dendritic cell-pulsing technology to enhance the effecicacy of a dendritic cell (DC)-based cancer vaccine.
SHK is a naphthoquinone compound that was isolated from root of traditional Chinese medicinal (TCM) herb, L. erythrorhizon. This dry root extract has been used for thousands of years in China, for treating macular eruptions, measles, sore-throat, carbuncles and burns, mainly externally, but it also can be used orally.
Dr. Yang’s team has previously demonstrated that SHK can exert anti- inflammatory activities via inhibiting the promoter activity of TNF-α and GM-CSF genes. SHK also interferes with TFN-α mRNA splicing. They further demonstrated that SK can down-regulate the expression of specific microRNAs related to epithelial-mesenchymal transition (EMT), likely resulting in expedited repair of mouse skin tissues. Most recently, they identified a protein, hnRNPA1, that can specifically bind SHK with very high affinity. Binding of SHK to hnRNPA1 was shown to affect nuclear pore transport of mRNAs and various RNA activities. This binding also was shown to result in tumor cell immunogenic cell death.
In the present study, Dr. Yang’s laboratory showed that SHK can render mouse mammary tumor cell necroptosis. SHK also activated tumor cell autophagy that in turn contributed to a sequence of events including upregulation of the ecto-form of damage-associated molecular patterns, DC activation, and augmented vaccine efficacy. Interruption of autophagic flux via chloroquine further upregulated ectoDAMP activity and resultant DC activation. Mice immunized by dying cell-pulsed DCs exerted potent efficacy in preventing mammary tumor metastasis as did the chemotherapy drug, doxorubicin (DX). Moreover, combined treatments of the SHK+DX drastically reduced the effective chemodrug dosage. These findings were published, as a Research paper-Translation entitled: Necroptosis promotes autophagy-dependent upregulation of DAMP and results in immunosurveillance in the journal Autophagy on Dec. 31 in 2017. The enhanced immunogenicity and vaccine efficacy via SHK and chloroquine cotreatment of tumor cells may thus constitute a compelling strategy for developing cancer vaccines via the use of a combinational drug treatment.
The first author of the article, Sheng-Yen Lin, received his Ph.D. in the Graduate Institute of Life Science, National Defense Medical Center. Dr. Tzoong-Shoon Wu intelligently and diligently helped direct this research approach. This work was supported by the grant from Ministry of Science and Technology of Taiwan and an Investigator Award by Academia Sinica.
Figure(A) The research team: Mr. Lin Sheng-Yen, Ph. D. student at the Graduate Institute of Life Sciences of National Defense Medical Center; Dr. Ning-Sun Yang, Distinguished Research Fellow, ABRC; Dr. Tzoong-Shoon Wu, Visiting scholar, IMB.
Figure(B) The research team's findings support the promising application of phytochemical shikonin on dendritic cell-based cancer vaccine for anti-tumor metastasis activity.
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