Liposome encapsulated curcumin-difluorinated (CDF) inhibits the growth of cisplatin resistant head and neck cancer stem cells.

Saroj K Basak,Alborz Zinabadi,Fazlul H Sarkar,Meera Srivastava,Victor M Duarte,Marilene B Wang,Natarajan Venkatesan,Clifton L Dalgard,James J Kang,Eri S Srivatsan,Arthur W Wu

doi:10.18632/oncotarget.4181

Abstract

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer, with 600,000 new cases every year worldwide. Although chemotherapeutics exist, five-year survival is only 50%. New strategies to overcome drug resistance are required to improve HNSCC treatment. Curcumin-difluorinated (CDF), a synthetic analog of curcumin, was packaged in liposomes and used to evaluate growth inhibition of cisplatin resistant HNSCC cell lines CCL-23R and UM-SCC-1R generated from the parental cell lines CCL-23 and UM-SCC-1 respectively. Growth inhibition in vitro and expression levels of the CD44 (cancer stem cell marker), cytokines, and growth factors were investigated after liposomal CDF treatment. The in vivo growth inhibitory effect of liposomal CDF was evaluated in the nude mice xenograft tumor model of UM-SCC-1R and the inhibition of CD44 was measured. Treatment of the resistant cell lines in vitro with liposomal CDF resulted in a statistically significant growth inhibition (p < 0.05). The nude mice xenograft study showed a statistically significant tumor growth inhibition of UM-SCC-1R cells and a reduction in the expression of CD44 (p < 0.05), indicating an inhibitory effect of liposomal CDF on CSCs. Our results demonstrate that delivery of CDF through liposomes may be an effective method for the treatment of cisplatin resistant HNSCC.

Highlights

Head and neck squamous cell carcinoma (HNSCC) affects 600,000 people worldwide annually, including 42,000 in the United States [1, 2]
It should be noted that all cells express CD44 in variable levels meaning both CD44lo and CD44hi cells exist within cancer cell lines and primary tumors
Cisplatin resistant head and neck cancer cell lines was isolated by treating cells in culture with gradually increasing concentrations of cisplatin, from 0.5 μg/mL to 6.0 μg/mL

Summary

Introduction

Head and neck squamous cell carcinoma (HNSCC) affects 600,000 people worldwide annually, including 42,000 in the United States [1, 2]. HNSCC includes oral, laryngeal and pharyngeal malignancies, with about 40% of these arising in the oral cavity. Current treatment methods for advanced head and neck cancer include radiation therapy, chemotherapy, and surgery. The five-year survival rate for all patients with head and neck cancer is 57%, and for patients with stage III and IV oral cancers the survival rate is 10-20% [3, 4]. Close to half of these (30 to 50%) patients develop local or regional recurrence and another 10-40% of patients develop second primary tumors of the aerodigestive tract due to field cancerization [5]

Methods

Results

Conclusion