title: Synergistic anti-oral cancer effects of UVC and methanolic extracts of Cryptocarya concinna roots via apoptosis, oxidative stress and DNA damage.
abstract: Purpose Radiation combined with natural products may improve the radiosensitivity of cancer cells. This study investigated the potential of a combined modality treatment with Ultraviolet C (UVC; wavelength range 200-280 nm) and our previously identified anti-oral cancer agent (methanolic extracts of Cryptocarya concinna roots; MECCrt) in oral cancer cells. Materials and methods The mechanism of the possible synergy of UVC and MECCrt was explored in terms of cell viability, cell cycle, apoptosis, reactive oxygen species (ROS), mitochondrial membrane potential (MitoMP), and DNA damage analyses. Results In cell viability (%) at 24 h treatment, the low doses of UVC (14 J/m(2)) and MECCrt (10 μg/ml) resulted in slight damage to human oral cancer Ca9-22 cells (83.2 and 80.4) but was less harmful to human oral normal HGF-1 cells (93.4 and 91.8, respectively). The combined treatment of UVC and MECCrt (UVC/MECCrt) had a lower viability (54.5%) than UVC or MECCrt alone in Ca9-22 cells but no showed significant change in HGF-1 cells. In Ca9-22 cells, the expression of flow cytometry-based apoptosis (sub-G1 phase, annexin V, and pancaspase assays) was significantly higher in UVC/MECCrt than in UVC or MECCrt alone (p < 0.0001). Using flow cytometry, intracellular ROS levels of UVC/MECCrt and MECCrt alone were higher than for UVC alone. MitoMP change and H2A histone family member X (γH2AX; H2AFX)-based DNA damage were synergistically inhibited and induced by MECCrt/UVC compared to its single treatment in Ca9-22 cells, respectively. Conclusion UVC plus MECCrt treatment had selective killing and synergistic anti-proliferative effects against oral cancer cells involving apoptosis, oxidative stress, and DNA damage. This combination therapy appears to have a great clinical potential against oral cancer cells.
authors.affiliation: a Department of Biomedical Science and Environmental Biology , Kaohsiung Medical University , Kaohsiung , Taiwan ;|b Institute of Medical Science and Technology, National Sun Yat-sen University , Kaohsiung , Taiwan ;|c Cancer Center, Kaohsiung Medical University Hospital, Kaohsiung Medical University , Kaohsiung , Taiwan ;|d Center for Research Resources and Development, Kaohsiung Medical University , Kaohsiung , Taiwan ;
authors.forename: Hsueh-Wei
authors.initials: HW
authors.lastname: Chang
authors.affiliation: e Department of Radiation Oncology, Faculty of Medicine, College of Medicine , Kaohsiung Medical University Hospital , Kaohsiung , Taiwan ;|f Department of Radiation Oncology , Kaohsiung Medical University , Kaohsiung , Taiwan ;|g Department of Radiation Oncology , Kaohsiung Municipal Ta-Tung Hospital , Kaohsiung , Taiwan ;
authors.forename: Jen-Yang
authors.initials: JY
authors.lastname: Tang
authors.affiliation: h Department of Oral and Maxillofacial Surgery , Chi-Mei Medical Center , Tainan ;|i School of Dentistry , Taipei Medical University , Taipei ;
authors.forename: Ching-Yu
authors.initials: CY
authors.lastname: Yen
authors.affiliation: j Graduate Institute of Natural Products, College of Pharmacy, Kaohsiung Medical University , Kaohsiung , Taiwan ;|k School of Pharmacy, College of Pharmacy , Kaohsiung Medical University , Kaohsiung , Taiwan ;
authors.forename: Hsun-Shuo
authors.initials: HS
authors.lastname: Chang
authors.affiliation: l Institute of Biomedical Science, National Sun Yat-Sen University , Kaohsiung , Taiwan.
authors.forename: Hurng-Wern
authors.initials: HW
authors.lastname: Huang
authors.affiliation: a Department of Biomedical Science and Environmental Biology , Kaohsiung Medical University , Kaohsiung , Taiwan ;
authors.forename: Yi-An
authors.initials: YA
authors.lastname: Chung
authors.affiliation: j Graduate Institute of Natural Products, College of Pharmacy, Kaohsiung Medical University , Kaohsiung , Taiwan ;|k School of Pharmacy, College of Pharmacy , Kaohsiung Medical University , Kaohsiung , Taiwan ;
authors.forename: Ih-Sheng
authors.initials: IS
authors.lastname: Chen
authors.affiliation: e Department of Radiation Oncology, Faculty of Medicine, College of Medicine , Kaohsiung Medical University Hospital , Kaohsiung , Taiwan ;|f Department of Radiation Oncology , Kaohsiung Medical University , Kaohsiung , Taiwan ;
authors.forename: Ming-Yii
authors.initials: MY
authors.lastname: Huang
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage; D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects; D045744:Cell Line, Tumor; D059248:Chemoradiotherapy / Q000379:methods; D031369:Cryptocarya / Q000737:chemistry*; D004249:DNA Damage; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D006801:Humans; D000432:Methanol / Q000737:chemistry; D009062:Mouth Neoplasms / Q000473:pathology / Q000503:physiopathology* / Q000628:therapy*; D018384:Oxidative Stress / Q000187:drug effects / Q000528:radiation effects; D010936:Plant Extracts / Q000008:administration & dosage / Q000737:chemistry*; D018517:Plant Roots / Q000737:chemistry*; D011836:Radiation Tolerance / Q000187:drug effects; D011879:Radiotherapy Dosage; D017382:Reactive Oxygen Species / Q000378:metabolism; D016896:Treatment Outcome; D000072258:Tumor Hypoxia / Q000187:drug effects / Q000528:radiation effects; D014467:Ultraviolet Therapy / Q000379:methods
chemical_list: D000970:Antineoplastic Agents; D010936:Plant Extracts; D017382:Reactive Oxygen Species; D000432:Methanol
keywords: DNA damage; ROS; Synergy; UVC; apoptosis; mitochondrial membrane potential; natural products; oral cancer