title: Realgar bioleaching solution suppress ras excessive activation by increasing ROS in Caenorhabditis elegans.
abstract: Although realgar bioleaching solution (RBS) has been proved to be a potential candidate for cancer therapy, the mechanisms of RBS anticancer are still far from being completely understood. Dosed with RBS in C. elegans, the multivulva phenotype resulting from oncogenic ras gain-of-function was inhibited in a dose dependent manner. It could be abrogated by concurrent treatment C. elegans with RBS and the radical scavenger DMSO. However, RBS could not induce DAF-16 nuclear translocation in TJ356 or the increase of HSP 16.2 expression in CL2070, which both could be aroused visible GFP fluorescent variation to represent for oxidative stress generation. Treatment C. elegans with superoxide anion generator paraquat, similar results were also obtained. Our results indicated that RBS suppress excessive activated ras by increasing reactive oxygen species (ROS) in C. elegans. Secondly, ROS induced by RBS significantly accumulated on a higher level in C. elegans with a mutational ras than that with wild ras, thus leading to oxidative stress on ras gain-of-function background rather than on normal ras context. Our results firstly demonstrated that using C. elegans as a model organism for evaluating prooxidant drug candidates for cancer therapy.
authors.affiliation: Institute of Microbiology and Biochemical Pharmacy, School of Pharmaceutics, Lanzhou University, Lanzhou, People's Republic of China, zhidej@lzu.edu.cn.
authors.forename: De Juan
authors.initials: de J
authors.lastname: Zhi
authors.forename: Na
authors.initials: N
authors.lastname: Feng
authors.forename: Dong Ling
authors.initials: DL
authors.lastname: Liu
authors.forename: Rong Li
authors.initials: RL
authors.lastname: Hou
authors.forename: Mei Zu
authors.initials: MZ
authors.lastname: Wang
authors.forename: Xiao Xia
authors.initials: XX
authors.lastname: Ding
authors.forename: Hong Yu
authors.initials: HY
authors.lastname: Li
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D001152:Arsenicals / Q000494:pharmacology*; D017173:Caenorhabditis elegans / Q000187:drug effects* / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D011905:Genes, ras / Q000187:drug effects* / Q000502:physiology; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D019999:Pharmaceutical Solutions / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013440:Sulfides / Q000494:pharmacology*
chemical_list: D001152:Arsenicals; D019999:Pharmaceutical Solutions; D017382:Reactive Oxygen Species; D013440:Sulfides; C058317:arsenic disulfide