GMI ablates cancer stemness and cisplatin resistance in oral carcinomas stem cells through IL-6/Stat3 signaling inhibition

// Tung Yuan Wang 1, * , Cheng-Chia Yu 1, 2, 3, * , Pei-Ling Hsieh 3 , Yi-Wen Liao 1 , Chuan-Hang Yu 1, 2 and Ming-Yung Chou 1, 2 1 School of Dentistry, Chung Shan Medical University, Taichung, Taiwan 2 Department of Dentistry, Chung Shan Medical University Hospital, Taichung, Taiwan 3 Institute of Oral Sciences, Chung Shan Medical University, Taichung, Taiwan * These authors have contributed equally to this work Correspondence to: Ming-Yung Chou, email: myc@csmu.edu.tw Chuan-Hang Yu, email: tao2008@csmu.edu.tw Keywords: oral squamous cell carcinomas, immunomodulatory protein GMI, cancer stem cells, chemoresistance, IL-6/Stat3 signaling Received: May 04, 2017      Accepted: June 19, 2017      Published: July 31, 2017 ABSTRACT Cancer stem cells (CSCs) have been identified to exert tumor-initiating ability, resulting in the recurrence, metastasis and chemoresistance of oral squamous cell carcinomas. In the present study, we showed that GMI, an immunomodulatory protein from Ganoderma microsporum , induc ed a cytotoxic effect in oral carcinomas stem cells (OCSCs). Treatment of GMI dose-dependently inhibited the expression of CSC markers, including ALDH1 activity and CD44 positivity. Moreover, GMI suppressed the self-renewal property, colony formation, migration, and invasion abilities as well as potentiated chemo-sensitivity in OCSCs. Our results suggested that the tumor suppressive effect of GMI was mediated through inhibition of IL-6/Stat3 signaling pathway. Furthermore, tumor growth was reduced in mice bearing xenograft tumors after oral administration of GMI. Taken together, we demonstrated the anti-CSC effect of GMI in oral cancer and GMI may serve as a natural cisplatin adjuvant to prevent cancer recurrence.