Inhibitory Effects Of Small Molecule Compound WYC-209 On Tumor Repopulating Cells

Malignant tumor is one of the leading causes of death in the world.Developing novel drugs that can abrogate the growth and metastasis of malignant tumors is a major challenge for cancer therapy.The notion of cancer stem cells hypothesizes that cancer stem cells play a critical role in the progression of cancer and the relapse after cancer therapy.However,the methods of selecting stem-cell-like cancer cells using cell surface markers remain highly controversial.Professor Ning Wang and his colleagues have developed a mechanical method of selecting and growing high tumourigenic cells,which are named tumor repopulating cells(TRCs).These TRCs have high tumorigenicity and when TRCs are injected as few as ten cells,they could form tumors in wild-type non-syngeneic mice.TRCs are resistant to conventional cancer drugs.Therefore it is critical to develop a new drug that can inhibit the proliferation of tumor repopulating cells.Here we describe a novel synthetic retinoid,namely WYC-209,which is able to inhibit proliferation of malignant murine melanoma tumour-repopulating cells in vitro via binding to retinoid acid receptor(RAR).10 μM WYC-209 could 100% inhibit proliferation of TRCs of human lung cnacer,breast cancer,ovarian cancer and melanoma in culture,much more effective than All-Trans-Retinoic Acid(ATRA)and Tazarotene.Importantly,10 μM WYC-209 could effectively inhibit B16-F1 melanoma metastases in C57bl/6 mice with no observable toxic side effects.Our findings demonstrate the promise of the new retinoid WYC-209 in treating malignant melanoma tumors with high efficacy and little toxicity.