title: Activation and Inhibition of ATM by Phytochemicals: Awakening and Sleeping the Guardian Angel Naturally.
abstract: Double-stranded breaks (DSBs) are cytotoxic DNA lesions caused by oxygen radicals, ionizing radiation, and radiomimetic chemicals. Increasing understanding of DNA damage signaling has provided an ever-expanding list of modulators reported to orchestrate DNA damage repair and ataxia telangiectasia mutated (ATM) is the master regulator and main transducer of the DSB response. Increasingly, it is being realized that DNA damage response is a synchronized and branched network that functionalizes different molecular cascades to activate special checkpoints, thus temporarily arresting progression of the cell cycle while damage is being assessed and processed. It is noteworthy that both nutrigenetics and nutrigenomics have revolutionized the field of molecular biology and rapidly accumulating experimental evidence has started to shed light on biological activities of a wide range of phytochemicals reported to modulate cell cycle, DNA repair, cell growth, differentiation and apoptosis as evidenced by cell-based studies. In this review, we have attempted to provide an overview of DNA damage signaling, how ATM signaling regulates tumor necrosis factors-related apoptosis inducing ligand (TRAIL)-induced intracellular network. We also illuminate on how resveratrol, epigallocatechin gallate, curcumin, jaceosidin, cucurbitacin, apigenin, genistein, and others trigger activation of ATM in different cancer cells as well as agents for ATM inactivation. Understanding the interplay of TRAIL-induced intracellular signaling and ATM modulation of downstream effectors is very important. This holds particularly for a reconceptualization of the apparently paradoxical roles and therapeutically targetable for enhancing the response to DNA damage-inducing therapy.
authors.affiliation: Laboratory for Translational Oncology and Personalized Medicine, Rashid Latif Medical College, Lahore, 54000, Pakistan.
authors.forename: Ammad Ahmad
authors.initials: AA
authors.lastname: Farooqi
authors.affiliation: Department of Medical Laboratory Science and Biotechnology, Kaohsiung Medical University, Kaohsiung, 80708, Taiwan.
authors.forename: Shyh-Jong
authors.initials: SJ
authors.lastname: Wu
authors.affiliation: Doctor Degree Program in Marine Biotechnology, National Sun Yat-sen University/Academia Sinica, Kaohsiung, 80424, Taiwan.
authors.forename: Yung-Ting
authors.initials: YT
authors.lastname: Chang
authors.affiliation: Department of Radiation Oncology, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung, 80145, Taiwan.|Department of Radiation Oncology, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, 80708, Taiwan.|Department of Radiation Oncology, Kaohsiung Medical University Hospital, Kaohsiung, 80708, Taiwan.
authors.forename: Jen-Yang
authors.initials: JY
authors.lastname: Tang
authors.affiliation: Department of Biomedical Science and Environmental Biology, Kaohsiung Medical University, Kaohsiung, 80708, Taiwan.
authors.forename: Kun-Tzu
authors.initials: KT
authors.lastname: Li
authors.affiliation: Institute of Biomedical and Genetic Engineering, KRL Hospital, Islamabad, 44000, Pakistan.
authors.forename: Muhammad
authors.initials: M
authors.lastname: Ismail
authors.affiliation: Department of Medical Laboratory Science and Biotechnology, Kaohsiung Medical University, Kaohsiung, 80708, Taiwan.|Department of Marine Biotechnology and Resources, National Sun Yat-sen University, Kaohsiung, 80424, Taiwan.
authors.forename: Chih-Chuang
authors.initials: CC
authors.lastname: Liaw
authors.affiliation: Department of Biomedical Science and Environmental Biology, Kaohsiung Medical University, Kaohsiung, 80708, Taiwan. runili@kmu.edu.tw.
authors.forename: Ruei-Nian
authors.initials: RN
authors.lastname: Li
authors.affiliation: Department of Biomedical Science and Environmental Biology, Kaohsiung Medical University, Kaohsiung, 80708, Taiwan. changhw@kmu.edu.tw.|Institute of Medical Science and Technology, National Sun Yat-sen University, Kaohsiung, 80424, Taiwan. changhw@kmu.edu.tw.|Cancer Center, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, 80708, Taiwan. changhw@kmu.edu.tw.|Research Center of Environmental Medicine, Kaohsiung Medical University, Kaohsiung, 80708, Taiwan. changhw@kmu.edu.tw.
authors.forename: Hsueh-Wei
authors.initials: HW
authors.lastname: Chang
mesh_terms: D000818:Animals; D064007:Ataxia Telangiectasia Mutated Proteins / Q000378:metabolism*; D053903:DNA Breaks, Double-Stranded / Q000187:drug effects*; D004249:DNA Damage / Q000187:drug effects*; D004260:DNA Repair / Q000187:drug effects*; D006801:Humans; D064209:Phytochemicals / Q000494:pharmacology*; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000378:metabolism
chemical_list: D064209:Phytochemicals; D053221:TNF-Related Apoptosis-Inducing Ligand; D025521:Tumor Suppressor Proteins; D064007:Ataxia Telangiectasia Mutated Proteins
keywords: ATM inducers; ATM inhibitors; Phytochemicals; p53