title: Amplification of oxidative stress by a dual stimuli-responsive hybrid drug enhances cancer cell death.
abstract: Cancer cells, compared with normal cells, are under oxidative stress associated with the increased generation of reactive oxygen species (ROS) including H2O2 and are also susceptible to further ROS insults. Cancer cells adapt to oxidative stress by upregulating antioxidant systems such as glutathione to counteract the damaging effects of ROS. Therefore, the elevation of oxidative stress preferentially in cancer cells by depleting glutathione or generating ROS is a logical therapeutic strategy for the development of anticancer drugs. Here we report a dual stimuli-responsive hybrid anticancer drug QCA, which can be activated by H2O2 and acidic pH to release glutathione-scavenging quinone methide and ROS-generating cinnamaldehyde, respectively, in cancer cells. Quinone methide and cinnamaldehyde act in a synergistic manner to amplify oxidative stress, leading to preferential killing of cancer cells in vitro and in vivo. We therefore anticipate that QCA has promising potential as an anticancer therapeutic agent.
authors.affiliation: Department of Polymer·Nano Science and Technology, Polymer Fusion Research Center, Chonbuk National University, Backje-daero 567, Jeonju 561-756, Korea.
authors.forename: Joungyoun
authors.initials: J
authors.lastname: Noh
authors.affiliation: Department of BIN Convergence Technology, Chonbuk National University, Backje-daero 567, Jeonju 561-756, Korea.
authors.forename: Byeongsu
authors.initials: B
authors.lastname: Kwon
authors.affiliation: Department of BIN Convergence Technology, Chonbuk National University, Backje-daero 567, Jeonju 561-756, Korea.
authors.forename: Eunji
authors.initials: E
authors.lastname: Han
authors.affiliation: Department of BIN Convergence Technology, Chonbuk National University, Backje-daero 567, Jeonju 561-756, Korea.
authors.forename: Minhyung
authors.initials: M
authors.lastname: Park
authors.affiliation: Department of BIN Convergence Technology, Chonbuk National University, Backje-daero 567, Jeonju 561-756, Korea.
authors.forename: Wonseok
authors.initials: W
authors.lastname: Yang
authors.affiliation: Department of BIN Convergence Technology, Chonbuk National University, Backje-daero 567, Jeonju 561-756, Korea.
authors.forename: Wooram
authors.initials: W
authors.lastname: Cho
authors.affiliation: Department of BIN Convergence Technology, Chonbuk National University, Backje-daero 567, Jeonju 561-756, Korea.
authors.forename: Wooyoung
authors.initials: W
authors.lastname: Yoo
authors.affiliation: Department of Polymer·Nano Science and Technology, Polymer Fusion Research Center, Chonbuk National University, Backje-daero 567, Jeonju 561-756, Korea.|Department of BIN Convergence Technology, Chonbuk National University, Backje-daero 567, Jeonju 561-756, Korea.
authors.forename: Gilson
authors.initials: G
authors.lastname: Khang
authors.affiliation: Department of Polymer·Nano Science and Technology, Polymer Fusion Research Center, Chonbuk National University, Backje-daero 567, Jeonju 561-756, Korea.|Department of BIN Convergence Technology, Chonbuk National University, Backje-daero 567, Jeonju 561-756, Korea.
authors.forename: Dongwon
authors.initials: D
authors.lastname: Lee
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D001896:Boron Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002460:Cell Line; D002853:Chromatography, Liquid / Q000379:methods; D053938:DNA Fragmentation; D004952:Esters / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006861:Hydrogen Peroxide; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009374:Neoplasms, Experimental / Q000188:drug therapy; D018384:Oxidative Stress / Q000187:drug effects*; D011897:Random Allocation; D017382:Reactive Oxygen Species; D053719:Tandem Mass Spectrometry
chemical_list: C000605235:4-(1,3,2-dioxaborinan-2-yl)benzyl ((5-methyl-2-styryl-1,3-dioxan-5-yl)methyl)carbonate; D000970:Antineoplastic Agents; D001896:Boron Compounds; D004952:Esters; D017382:Reactive Oxygen Species; D006861:Hydrogen Peroxide