title: Liposome encapsulated curcumin-difluorinated (CDF) inhibits the growth of cisplatin resistant head and neck cancer stem cells.
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.
authors.affiliation: Department of Surgery, VA Greater Los Angeles Healthcare System, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, CA, USA.
authors.forename: Saroj K
authors.initials: SK
authors.lastname: Basak
authors.affiliation: Department of Surgery, VA Greater Los Angeles Healthcare System, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, CA, USA.
authors.forename: Alborz
authors.initials: A
authors.lastname: Zinabadi
authors.affiliation: Department of Surgery, VA Greater Los Angeles Healthcare System, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, CA, USA.
authors.forename: Arthur W
authors.initials: AW
authors.lastname: Wu
authors.affiliation: Department of Surgery, VA Greater Los Angeles Healthcare System, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, CA, USA.
authors.forename: Natarajan
authors.initials: N
authors.lastname: Venkatesan
authors.affiliation: Department of Surgery, VA Greater Los Angeles Healthcare System, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, CA, USA.|Department of Head and Neck Surgery, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, CA, USA.
authors.forename: Victor M
authors.initials: VM
authors.lastname: Duarte
authors.affiliation: Department of Surgery, VA Greater Los Angeles Healthcare System, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, CA, USA.
authors.forename: James J
authors.initials: JJ
authors.lastname: Kang
authors.affiliation: Departments of Anatomy, Physiology and Genetics, Molecular and Cell Biology, Uniformed Services University, Bethesda, MD, USA.
authors.forename: Clifton L
authors.initials: CL
authors.lastname: Dalgard
authors.affiliation: Departments of Anatomy, Physiology and Genetics, Molecular and Cell Biology, Uniformed Services University, Bethesda, MD, USA.
authors.forename: Meera
authors.initials: M
authors.lastname: Srivastava
authors.affiliation: Karmanos Cancer Institute, Wayne State University, Detroit, MI, USA.
authors.forename: Fazlul H
authors.initials: FH
authors.lastname: Sarkar
authors.affiliation: Department of Surgery, VA Greater Los Angeles Healthcare System, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, CA, USA.|Department of Head and Neck Surgery, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, CA, USA.|Jonsson Comprehensive Cancer Center, University of California Los Angeles, Los Angeles, CA, USA.
authors.forename: Marilene B
authors.initials: MB
authors.lastname: Wang
authors.affiliation: Department of Surgery, VA Greater Los Angeles Healthcare System, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, CA, USA.|Jonsson Comprehensive Cancer Center, University of California Los Angeles, Los Angeles, CA, USA.
authors.forename: Eri S
authors.initials: ES
authors.lastname: Srivatsan
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D002945:Cisplatin / Q000494:pharmacology; D003474:Curcumin / Q000031:analogs & derivatives / Q000494:pharmacology*; D016207:Cytokines / Q000378:metabolism; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D006801:Humans; D018960:Hyaluronan Receptors / Q000235:genetics; D006845:Hydrocarbons, Fluorinated / Q000494:pharmacology*; D008081:Liposomes; D008819:Mice, Nude; D014411:Neoplastic Stem Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D047368:Tumor Burden / Q000187:drug effects / Q000235:genetics; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D016207:Cytokines; D018960:Hyaluronan Receptors; D006845:Hydrocarbons, Fluorinated; D008081:Liposomes; D003474:Curcumin; D002945:Cisplatin
keywords: cancer stem cell (CSC); cisplatin; curcumin-difluorinated (CDF); drug resistance; head and neck cancer