title: Near-Infrared Fluorescence Probe for Monitoring the Metabolic Products of Vitamin C in HepG2 Cells under Normoxia and Hypoxia.
abstract: Vitamin C (ascorbic acid; AA) is a well-known reducing agent and has been evaluated for its antitumor activity. However, the mechanism for its antitumor action remains unclear. Tracking the metabolism of AA may help to elucidate its antitumor mechanism. In this study, a near-infrared fluorescent probe (Arg-Cy) for monitoring the metabolic products of AA in living cells was developed based on the reaction of the guanidine group in Arg-Cy with the adjacent diketone involved in the metabolites of AA. Consequently, the probe can respond to L-xylosone, a metabolite of AA, with high selectivity and sensitivity and was successfully used to visualize the real-time changes of L-xylosone levels in living cells incubated under normoxic conditions. Considering that the tumor microenvironment suffers from hypoxia, the L-xylosone levels in the process of HepG2 cell death induced by pharmacological doses of AA were also monitored under hypoxic conditions. Surprisingly, no obvious fluorescence change appeared during this process. Furthermore, detection of the intracellular redox state using a reported H2O2 probe confirmed that AA can be metabolized to L-xylosone only under normoxic conditions due to the oxidative stress, but not under hypoxic conditions. Therefore, we hypothesize that the mechanism for cell death induced by AA under hypoxia is different from that under normoxia. Thus, the developed probe can provide a tool for monitoring the metabolism of AA and may help to clarify the mechanism for the antitumor activity of vitamin C in the tumor microenvironment.
authors.affiliation: †Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong, Key Laboratory of Molecular and Nano Probes, Ministry of Education, Shandong Provincial Key Laboratory of Clean Production of Fine Chemicals, College of Chemistry, Chemical Engineering and Materials Science, Shandong Normal University, Jinan 250014, People's Republic of China.|‡Department of Pharmaceutical Sciences, Binzhou Medical University, Shandong Yantai 264003, People's Republic of China.
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Pan
authors.affiliation: †Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong, Key Laboratory of Molecular and Nano Probes, Ministry of Education, Shandong Provincial Key Laboratory of Clean Production of Fine Chemicals, College of Chemistry, Chemical Engineering and Materials Science, Shandong Normal University, Jinan 250014, People's Republic of China.
authors.forename: Xiaoting
authors.initials: X
authors.lastname: Wang
authors.affiliation: †Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong, Key Laboratory of Molecular and Nano Probes, Ministry of Education, Shandong Provincial Key Laboratory of Clean Production of Fine Chemicals, College of Chemistry, Chemical Engineering and Materials Science, Shandong Normal University, Jinan 250014, People's Republic of China.
authors.forename: Liyong
authors.initials: L
authors.lastname: Wang
authors.affiliation: †Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong, Key Laboratory of Molecular and Nano Probes, Ministry of Education, Shandong Provincial Key Laboratory of Clean Production of Fine Chemicals, College of Chemistry, Chemical Engineering and Materials Science, Shandong Normal University, Jinan 250014, People's Republic of China.
authors.forename: Kehua
authors.initials: K
authors.lastname: Xu
authors.affiliation: †Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong, Key Laboratory of Molecular and Nano Probes, Ministry of Education, Shandong Provincial Key Laboratory of Clean Production of Fine Chemicals, College of Chemistry, Chemical Engineering and Materials Science, Shandong Normal University, Jinan 250014, People's Republic of China.
authors.forename: Fanpeng
authors.initials: F
authors.lastname: Kong
authors.affiliation: †Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong, Key Laboratory of Molecular and Nano Probes, Ministry of Education, Shandong Provincial Key Laboratory of Clean Production of Fine Chemicals, College of Chemistry, Chemical Engineering and Materials Science, Shandong Normal University, Jinan 250014, People's Republic of China.
authors.forename: Bo
authors.initials: B
authors.lastname: Tang
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D001205:Ascorbic Acid / Q000032:analysis* / Q000737:chemistry; D015687:Cell Hypoxia; D004151:Dipeptides / Q000737:chemistry; D005456:Fluorescent Dyes / Q000737:chemistry / Q000378:metabolism; D056945:Hep G2 Cells; D006801:Humans; D006861:Hydrogen Peroxide / Q000737:chemistry / Q000633:toxicity; D007661:Ketoses / Q000737:chemistry / Q000378:metabolism; D008856:Microscopy, Fluorescence; D021241:Spectrometry, Mass, Electrospray Ionization
chemical_list: D004151:Dipeptides; D005456:Fluorescent Dyes; D007661:Ketoses; C067906:threo-pentos-2-ulose; D006861:Hydrogen Peroxide; D001205:Ascorbic Acid