Abstract
Cancer stem cells (CSCs) are cells that drive tumorigenesis, contributing to metastasis and cancer recurrence as well as resistance to chemotherapy of oral squamous cell carcinomas (OSCC). Therefore, approaches to target CSCs become the subject of intense research for cancer therapy. In this study, we demonstrated that isoliquiritigenin, a chalcone-type flavonoid isolated from licorice root, exhibited more toxicity in oral cancer stem cells (OSCC-CSCs) compared to normal cells. Treatment of isoliquiritigenin not only inhibited the self-renewal ability but also reduced the expression of CSC markers, including the ALDH1 and CD44. In addition, the capacities of OSCC-CSCs to invade, metastasize and grow into a colony were suppressed by isoliquiritigenin. Most importantly, we showed that isoliquiritigenin potentiated chemotherapy along with downregulated expression of an ABC transporter that is associated with drug resistance, ABCG2. Moreover, a combination of isoliquiritigenin and Cisplatin significantly repressed the invasion and colony formation abilities of OSCC-CSCs. Our results suggested that administration of isoliquiritigenin reduced the protein expression of mRNA and membrane GRP78, a critical mediator of tumor biology. Overexpression of GRP78 reversed the inhibitory effect of isoliquiritigenin on OSCC-CSCs. Furthermore, isoliquiritigenin retarded the tumor growth in nude mice bearing OSCC xenografts. Taken together, these findings showed that isoliquiritigenin is an effective natural compound that can serve as an adjunct to chemotherapy for OSCC.
Highlights
Head and neck squamous cell carcinoma (HNSCC) is one of the most prevalent and aggressive malignancies worldwide with a dismal prognosis
We demonstrated that isoliquiritigenin, a chalcone-type flavonoid isolated from licorice root, exhibited more toxicity in oral cancer stem cells (OSCC-Cancer stem cells (CSCs)) compared to normal cells
Our results showed that maintenance of self-renewal in these two oral squamous cell carcinomas (OSCC)-CSCs was inversely affected as the concentration of isoliquiritigenin increased (Figure 1B), suggesting the potential anti-OSCC-CSCs effect of ISL
Summary
Head and neck squamous cell carcinoma (HNSCC) is one of the most prevalent and aggressive malignancies worldwide with a dismal prognosis. The majority of HNSCC is oral squamous cell carcinoma (OSCC) that arises from the mucosal surfaces of the oral cavity, lateral border of the tongue, and floor of the mouth. Over the past few years, the survival rate is still far from satisfactory despite continuous efforts to develop effective treatments [1]. Recurrence of cancer after chemotherapy remains a major problem that needs to be solved [2]. A recent study has revealed that 3-year overall survival rate of advanced OSCC patients with recurrent tumors was less www.impactjournals.com/oncotarget than 30% [3]. It is imperative to identify targets and develop novel therapeutic strategies for OSCC
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
