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Although, oral cancer therapies have been developed for decades, patient survival rates have not changed. Side effects of chemotherapy and radiotherapy reduce quality of life of patients and it remains difficult to treat oral cancers due to the presence of cancer stem cells (CSCs) that cause recurrence and metastasis. Therefore, we search for natural products that affect oral cancer cells including oral cancer stem cells. In the present study, we investigated the anticancer effects of Raphanus sativus L. seed (RSLS) extracts on oral squamous cell carcinoma KB cells and CSC-like KBCD133+ cells. CD133 plays an important role in CSCs and physically binds to β-catenin to activate the β-catenin signaling targets. Therefore, a natural extract that can inhibit β-catenin act in may be effective anticancer drug acquiring CSC. Of the natural product extract candidates, RSLS extracts induced apoptosis in KB and KBCD133+ cells and inhibited nuclear translocation of β-catenin cell migration and invasion rates. Treatment of RSLS extracts resulted in increases of Axin and it leds to reductions of β-catenin in KB and KBCD133+ cells. Hence, the result suggests that RSLS are potential candidate for anticancer drug against oral cancer cells and CSCs. CSC cancer stem cells OSCC squamous cell carcinoma cells RSLS Raphanus sativus L. seed. [ABSTRACT FROM AUTHOR]