title: A new 2-pyrone derivative, 5-bromo-3-(3-hydroxyprop-1-ynyl)-2H-pyran-2-one, synergistically enhances radiation sensitivity in human cervical cancer cells.
abstract: Radiation resistance can be overcome by a combination treatment with chemical modifiers. Here, we showed that treatment with 5-bromo-3-(3-hydroxyprop-1-ynyl)-2H-pyran-2-one (BHP), a new 2-pyrone derivative, in combination with ionizing radiation enhances the sensitivity of human cervical cancer cells to ionizing radiation through overproduction of reactive oxygen species (ROS). The combined treatment with BHP and ionizing radiation caused a decrease in clonogenic survival and an increase in apoptotic cell death in cervical cancer cells. The combined treatment promoted conformational activation of Bax and led to mitochondrial apoptotic cell death. The combination treatment also induced a marked increase in intracellular ROS level. Inhibition of ROS attenuated the radiosensitizing effect of BHP, concurrent with a decrease in Bax activation, a decrease in mitochondrial cell death, and an increase in clonogenic survival. These results indicate that BHP synergistically enhances sensitivity of human cervical cancer cells to ionizing radiation through elevation of intracellular ROS and that ROS-dependent Bax activation is critically involved in the increase in apoptotic cell death induced by the combined treatment with BHP and ionizing radiation.
authors.affiliation: Department of Chemistry and Research Institute for Natural Sciences, Hanyang University, Seoul, Korea.
authors.forename: Soo-Jung
authors.initials: SJ
authors.lastname: Woo
authors.forename: Min-Jung
authors.initials: MJ
authors.lastname: Kim
authors.forename: Rae-Kwon
authors.initials: RK
authors.lastname: Kim
authors.forename: Chang-Hwan
authors.initials: CH
authors.lastname: Yoon
authors.forename: Eun-Jung
authors.initials: EJ
authors.lastname: Lim
authors.forename: Sungkwan
authors.initials: S
authors.lastname: An
authors.forename: Yongjoon
authors.initials: Y
authors.lastname: Suh
authors.forename: Ji-Young
authors.initials: JY
authors.lastname: Song
authors.forename: In Gyu
authors.initials: IG
authors.lastname: Kim
authors.forename: Cheon-Gyu
authors.initials: CG
authors.lastname: Cho
authors.forename: Su-Jae
authors.initials: SJ
authors.lastname: Lee
mesh_terms: D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects; D003131:Combined Modality Therapy; D005260:Female; D006801:Humans; D008928:Mitochondria / Q000187:drug effects / Q000528:radiation effects; D011714:Pyrans; D011753:Pyrones / Q000494:pharmacology*; D011836:Radiation Tolerance / Q000187:drug effects; D011839:Radiation, Ionizing; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D014407:Tumor Cells, Cultured; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: C572758:5-bromo-3-(3-hydroxyprop-1-ynyl)-2H-pyran-2-one; C494826:BAX protein, human; D011714:Pyrans; D011753:Pyrones; D011838:Radiation-Sensitizing Agents; D017382:Reactive Oxygen Species; D051028:bcl-2-Associated X Protein