SCREENING OF Β-CATENIN INHIBITOR FROM MEDICINAL PLANT EXTRACTS FOR INTRACTABLE RECURRENT ORAL CANCER

Abstract

Objectives Recent progress in malignant tumors has revealed cancer stem cells (CSC) can be the key contributors in tumor ignition, progression, and chemoradiotherapy recurrence. CD133 is a prognostic marker of survival in squamous cell carcinoma (SCC) including OSCC. CD133 can physically associate as a ternary complex with HDAC6 and the central molecule of the canonical Wnt signaling pathway, β-catenin. This association stabilizes β-catenin and leads to activation of β-catenin signaling targets in colon and ovarian cancer cell lines. Therefore, given that CD133 marks progenitor cells and strongly related with β-catenin activation, targeting β-catenin may be a means to treat multiple cancer types in CD133+ CSC-like cells. In this study, we confirmed that b-catenin was also overexpressed in KBCD133+ cells which acquired CSC-like characteristics than KB cells. Therefore we hypothesized a natural extract capable of inhibiting the activity of β-catenin can effectively inhibit the cancer progression of OSCC which acquired CSC-like characteristics. Findings We measured β-catenin activity of 54 plant extracts to select new candidates with β-catenin inhibitory effect. We have found 5 candidates showed significant inhibited β-catenin activities and Raphanus sativus L. seed (RSLS) extracts effectively induces cell apoptosis in KB as well as KBCD133+ cells. We also investigated that RSLS has strong inhibit nuclear localization of β-catenin, EMT via Axin/GSK-3β/β-catenin pathway. Conclusions We propose that RSLS can be used as a new alternative chemotherapeutic for the treatment of intractable recurrent oral cancer.