title: Carboplatin synergistically triggers the efficacy of photodynamic therapy via caspase 3-, 8-, and 12-dependent pathways in human anaplastic thyroid cancer cells.
abstract: Anaplastic thyroid cancer is one of the most aggressive forms of malignancies which grow very rapidly. Several conventional methods have been applied for the treatment of anaplastic thyroid cancer, but most of them were not successful in complete recovery of the patients. Therefore, a combination of two or more conventional modalities is being applied nowadays for the treatment of this type of cancer. In this present study, the combination of photodynamic therapy (PDT) and chemotherapy has been studied in anaplastic thyroid cancer. Human anaplastic thyroid cancer cells FRO were treated with a chemotherapy drug, carboplatin (cis-diammine-1,1-cyclobutanedicarboxyl-ateplatinum II (CBDCA)), and radachlorin-mediated PDT individually and in combination. Several parameters like cytotoxicity assay by MTT, apoptosis study by annexin V and propidium iodide, cell cycle analysis by flow cytometry, confocal microscopic study, and Western blot analysis for different apoptosis-related proteins like Bax, cytochrome c, caspases 3, 9, 8, and 12, etc. were studied to check the efficacy of the combination treatment as well as to find out the mechanism of this enhanced efficacy. Results showed that both PDT and CBDCA can induce apoptosis in FRO cells. However, a synergistic efficacy was observed when the cells were treated with CBDCA and PDT in combination. Changes in mitochondrial membrane potential and an increase in reactive oxygen species generation were observed in combination treatments. The enhanced expression of different apoptotic pathway-related proteins like Bax, cytochrome c, caspase 3, caspase 8, caspase 12, etc. also confirmed the higher efficacy of combination treatment. Therefore, with this combination treatment, not only a higher efficacy can be achieved but also the effective dose of the chemotherapy drug can be reduced, and hence, the adverse side effects of the chemotherapy drugs can also be controlled.
authors.affiliation: Beckman Laser Institute Korea, Dankook University, 29-1, Anseo-dong, Cheonan, Chungnam, Republic of Korea, 330-714.
authors.forename: Raktim
authors.initials: R
authors.lastname: Biswas
authors.forename: Phil-Sang
authors.initials: PS
authors.lastname: Chung
authors.forename: Jeong Hwan
authors.initials: JH
authors.lastname: Moon
authors.forename: Seung-Ha
authors.initials: SH
authors.lastname: Lee
authors.forename: Jin-Chul
authors.initials: JC
authors.lastname: Ahn
mesh_terms: D017304:Annexin A5 / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D016190:Carboplatin / Q000494:pharmacology / Q000627:therapeutic use*; D053454:Caspase 12 / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D053181:Caspase 8 / Q000378:metabolism; D020169:Caspases / Q000378:metabolism*; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003131:Combined Modality Therapy; D045304:Cytochromes c; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects; D005434:Flow Cytometry; D016650:Fluorescein-5-isothiocyanate / Q000378:metabolism; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D024101:Mitochondrial Proteins / Q000378:metabolism; D010778:Photochemotherapy; D011419:Propidium / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D065646:Thyroid Carcinoma, Anaplastic / Q000188:drug therapy* / Q000201:enzymology* / Q000473:pathology
chemical_list: D017304:Annexin A5; D024101:Mitochondrial Proteins; D017382:Reactive Oxygen Species; D011419:Propidium; D045304:Cytochromes c; D016190:Carboplatin; D053454:Caspase 12; D053148:Caspase 3; D053181:Caspase 8; D020169:Caspases; D016650:Fluorescein-5-isothiocyanate