title: Ambient UVA-induced expression of p53 and apoptosis in human skin melanoma A375 cell line by quinine.
abstract: This study aimed to analyze the phototoxic mechanism and photostability of quinine in human skin cell line A375 under ambient intensities of UVA (320-400 nm). Photosensitized quinine produced a photoproduct 6-methoxy-quinoline-4-ylmethyl-oxonium identified through LC-MS/MS. Generation of (1)O2, O2(•-), and (•)OH was measured and further substantiated through their respective quenchers. Photosensitized Quinine (Q) caused degradation of 2-deoxyguanosine, the most sensitive nucleotide to UV radiation. The intracellular ROS was increased in a concentration-dependent manner. Significant reduction in metabolic status measured in terms of cell viability (54%) at 25 μg mL(-1) was observed through MTT assay. Results of MTT assay accord NRU assay. Single strand DNA breaks and apoptosis were increased significantly (P < 0.01) as observed through comet assay and EB/AO double staining. Photosensitized quinine caused cells to arrest in G2 phase of cell cycle and induced apoptosis (5.08%) as revealed through FACS. Real-Time PCR showed upregulation of p21 (4.56 folds) and p53 (2.811 folds) genes expression. Thus, our study suggests that generation of reactive oxygen species by quinine under ambient intensity of UVA may result into deleterious phototoxic effects among human population.
authors: Photobiology Division, CSIR-Indian Institute of Toxicology Research, Lucknow, India.
authors: Neera
authors: N
authors: Yadav
authors: Ashish
authors: A
authors: Dwivedi
authors: Syed Faiz
authors: SF
authors: Mujtaba
authors: Hari Narayan
authors: HN
authors: Kushwaha
authors: Shio Kumar
authors: SK
authors: Singh
authors: Ratan Singh
authors: RS
authors: Ray
mesh_terms: D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects; D059447:Cell Cycle Checkpoints; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D020552:Comet Assay; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics* / Q000378:metabolism; D053904:DNA Breaks, Single-Stranded / Q000187:drug effects / Q000528:radiation effects; D006801:Humans; D017665:Hydroxyl Radical / Q000378:metabolism; D008545:Melanoma; D009336:Necrosis; D011803:Quinine / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D012867:Skin / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology / Q000528:radiation effects; D012878:Skin Neoplasms; D013481:Superoxides / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000378:metabolism; D014466:Ultraviolet Rays; D015854:Up-Regulation
chemical_list: C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D017382:Reactive Oxygen Species; D016159:Tumor Suppressor Protein p53; D013481:Superoxides; D017665:Hydroxyl Radical; D011803:Quinine