title: Modulation of EGFR and ROS induced cytochrome c release by combination of photodynamic therapy and carboplatin in human cultured head and neck cancer cells and tumor xenograft in nude mice.
abstract: Photodynamic therapy in combination with different treatment modalities has been evaluated to study the mechanism of cellular cytotoxicity and apoptosis in various forms of cancer. In the present study, human head and neck cancer cells were treated with radachlorin mediated photodynamic therapy and the chemotherapy drug, carboplatin singly or in combination. Several parameters were studied to check the enhanced cytotoxicity of combination therapy at different time interval. From the cell viability study by MTT assay, a 22% decrease in cell viability was observed in combination treatment. This enhanced activity of combination treatment was confirmed by cell migration assay and Hoechst PI staining. Generation of reactive oxygen species was observed and found to be higher than that of individual treatments. Cytochrome c was found to be released from mitochondria that also induced the enhance efficacy in combination treatment. The expression of other proteins like EGFR and PARP was also modulated with the time of incubation after treatment. In the tumor xenograft study in nude mouse model, the carboplatin treated group did not show any noticeable changes in tumor volume whereas tumor volume was reduced in PDT and the combination group. Though the difference in the reduction of the tumor size was not significant between PDT and combination group, there was a difference in the expression of EGFR between these two groups. Histologic study of the inhibition in tumor growth was also performed. Therefore, this study may provide an avenue of combating head and neck cancer by a combination of conventional chemotherapy and PDT.
authors.affiliation: Department of Molecular and Medical Pharmacology, University of California Los Angeles, Los Angeles, CA, USA.
authors.forename: Heejun
authors.initials: H
authors.lastname: Hwang
authors.forename: Raktim
authors.initials: R
authors.lastname: Biswas
authors.forename: Phil-Sang
authors.initials: PS
authors.lastname: Chung
authors.forename: Jin-Chul
authors.initials: JC
authors.lastname: Ahn
mesh_terms: D000818:Animals; D016190:Carboplatin / Q000494:pharmacology / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003131:Combined Modality Therapy; D045304:Cytochromes c / Q000378:metabolism*; D004357:Drug Synergism; D066246:ErbB Receptors / Q000378:metabolism*; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000494:pharmacology / Q000627:therapeutic use*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D014183:Transplantation, Heterologous
chemical_list: D017319:Photosensitizing Agents; D017382:Reactive Oxygen Species; D045304:Cytochromes c; D016190:Carboplatin; D066246:ErbB Receptors
keywords: Carboplatin; Combination therapy; PDT; ROS; Radachlorin