Liposome encapsulated curcumin-difluorinated (CDF) inhibits the growth of cisplatin resistant head and neck cancer stem cells
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Saroj K. Basak1, Alborz Zinabadi1, Arthur W. Wu1, Natarajan Venkatesan1, Victor M. Duarte1,2, James J. Kang1, Clifton L. Dalgard3, Meera Srivastava3, Fazlul H. Sarkar4, Marilene B. Wang1,2,5 and Eri S. Srivatsan1,5
1 Department of Surgery, VA Greater Los Angeles Healthcare System, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, CA, USA
2 Department of Head and Neck Surgery, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, CA, USA
3 Departments of Anatomy, Physiology and Genetics, Molecular and Cell Biology, Uniformed Services University, Bethesda, MD, USA
4 Karmanos Cancer Institute, Wayne State University, Detroit, MI, USA
5 Jonsson Comprehensive Cancer Center, University of California Los Angeles, Los Angeles, CA, USA
Eri S. Srivatsan, email:
Keywords: head and neck cancer, cisplatin, drug resistance, curcumin-difluorinated (CDF), cancer stem cell (CSC)
Received: March 16, 2015 Accepted: May 10, 2015 Published: May 19, 2015
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.
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