title: 1,8-dihydroxy-3-acetyl-6-methyl-9,10 anthraquinone exhibits a potent radiosensitizing effect with induced oncosis in human nasopharyngeal carcinoma cells.
abstract: 1,8‑dihydroxy‑3‑acetyl‑6‑methyl‑9,10 anthraquinone (DAMA) was synthesized from emodin. In the present study, the activity and the oncosis‑like mechanism of DAMA‑enhanced nasopharyngeal carcinoma (NPC) cell sensitivity to ionizing radiation was examined. The results demonstrated that DAMA has a 1.46‑fold radiosensitisation activity for nasopharyngeal carcinoma CNE 1 cells with a non‑cytotoxic concentration of 10 µg/ml DAMA combined with 2 Gy. Following treatment of DAMA combined with radiation, CNE‑1 cells revealed severe cytoplasmic swelling and vacuolization, swollen mitochondria and dilation of the nuclei without chromatin condensation, yielding a typical morphology of oncosis. Oncosis‑related gene expression of ATP synthase F0 subunit 6, chromatin modifying protein 6 and cyclophilin D mRNA increased significantly in the 8 Gy radiation group and the 2 Gy radiation combined with DAMA group. A significant decrease of ATP synthase protein 8 mRNA was observed and the levels of intracellular ATP were also reduced. In addition, the levels of intracellular Ca2+ were increased. In conclusion, DAMA is a potent radiation sensitizer in nasopharyngeal carcinoma cells and mediates its radiosensitisation via oncosis.
authors.affiliation: Department of Pharmaceutical Analysis, College of Pharmacy, Guangxi Medical University, Nanning, Guangxi 530021, P.R. China.
authors.forename: Huaxin
authors.initials: H
authors.lastname: Hou
authors.affiliation: Department of Cellular Biology, The Medical Scientific Research Centre of Guangxi Medical University, Nanning, Guangxi 530021, P.R. China.
authors.forename: Danrong
authors.initials: D
authors.lastname: Li
authors.affiliation: Department of Pharmaceutical Analysis, College of Pharmacy, Guangxi Medical University, Nanning, Guangxi 530021, P.R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Jiang
authors.affiliation: Department of Pharmaceutical Analysis, College of Pharmacy, Guangxi Medical University, Nanning, Guangxi 530021, P.R. China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Liang
authors.affiliation: Department of Pharmaceutical Analysis, College of Pharmacy, Guangxi Medical University, Nanning, Guangxi 530021, P.R. China.
authors.forename: Donglian
authors.initials: D
authors.lastname: Chen
authors.affiliation: Department of Pharmaceutical Analysis, College of Pharmacy, Guangxi Medical University, Nanning, Guangxi 530021, P.R. China.
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Mo
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000880:Anthraquinones / Q000737:chemistry / Q000633:toxicity*; D017209:Apoptosis / Q000187:drug effects* / Q000528:radiation effects; D002118:Calcium / Q000378:metabolism; D002277:Carcinoma; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000187:drug effects / Q000648:ultrastructure; D000081406:Peptidyl-Prolyl Isomerase F; D021983:Cyclophilins / Q000235:genetics / Q000378:metabolism; D056827:Endosomal Sorting Complexes Required for Transport / Q000235:genetics / Q000378:metabolism; D005720:Gamma Rays; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects / Q000528:radiation effects; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D025261:Mitochondrial Proton-Translocating ATPases / Q000235:genetics / Q000378:metabolism; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000378:metabolism / Q000473:pathology; D015388:Organelles / Q000187:drug effects / Q000648:ultrastructure; D011838:Radiation-Sensitizing Agents / Q000737:chemistry / Q000633:toxicity*
chemical_list: C000595056:3-acetyl-1,8-dihydroxy-6-methyl-9,10-anthraquinone; D000880:Anthraquinones; C481528:CHMP6 protein, human; D000081406:Peptidyl-Prolyl Isomerase F; D056827:Endosomal Sorting Complexes Required for Transport; C501005:MT-ATP6 protein, human; D011838:Radiation-Sensitizing Agents; C042834:9,10-anthraquinone; D000255:Adenosine Triphosphate; C513300:MT-ATP8 protein, human; D025261:Mitochondrial Proton-Translocating ATPases; D021983:Cyclophilins; D002118:Calcium