Journal of Oncology Translational Research

SHIKONIN ENHANCES THE ANTITUMOR EFFECTS OF CABAZITAXEL IN PROSTATE CANCER STEM CELLS

Abstract

Lili Wang, Birgit Stadlbauer and Heike Pohla

Cancer stem cells (CSCs) are a small population among cancer cells, defined as capable of self-renewal, and driving tumor growth, metastasis, and therapeutic
relapse. The development of therapeutic strategies to target CSCs is of great importance to prevent tumor metastasis and relapse. In the last decade, traditional
Chinese medicines (TCM) have been increasingly used as an additional treatment strategy following surgery, chemotherapy, or radiation therapy for cancer
patients worldwide, and accumulating evidences have been shown that some of these substances have significant effects also on CSCs. In our studies the
effect of shikonin on prostate CSCs was analysed. Sphere formation assay was used to generate prostate CSCs. Celltiter blue assay and Celltiter 96 aqueous
one solution proliferation assay were used to evaluate the viability and proliferation. To measure migration and invasion the scratch wound healing assay and
transwell assays were applied. Typical CSC markers were analysed by flow cytometry and quantitative RT-PCR. Furthermore, to characterize the apoptotic
process reactive oxygen species (ROS) and mitochondrial membrane potential were determined. Shikonin inhibits the viability and proliferation of prostate CSCs
in a dose-dependent manner and enhances the effect of cabazitaxel, which is a secondline chemotherapeutic drug in advanced prostate cancer concerning
viability, proliferation, apoptosis, migration, and invasion. Shikonin induces CSC apoptosis through inducing ROS generation, and disrupting the mitochondrial
membrane potential. Furthermore, shikonin suppresses the expression of ALDH3A1 and ABCG2 in prostate CSCs, two markers related to drug-resistance. In
conclusion, shikonin enhances the cytotoxic activity of cabazitaxel in prostate CSCs. Further studies must show to what extent shikonin is also able to abolish
the resistance of tumor cells to cabazitaxel.