Monday, 26 October 2015

Activation and Inhibition of ATM by Phytochemicals: Awakening and Sleeping the Guardian Angel Naturally

Volume 63, Issue 5, 19 June 2015, Pages 357-366

Laboratory for Translational Oncology and Personalized Medicine, Rashid Latif Medical College, Lahore, Pakistan
Department of Medical Laboratory Science and Biotechnology, Kaohsiung Medical University, Kaohsiung, Taiwan
Doctor Degree Program in Marine Biotechnology, National Sun Yat-sen University/Academia Sinica, Kaohsiung, Taiwan


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. © 2015, L. Hirszfeld Institute of Immunology and Experimental Therapy, Wroclaw, Poland.

Author keywords

ATM inducers; ATM inhibitors; p53; Phytochemicals

Indexed keywords

EMTREE drug terms: apigenin; Artemisia princeps extract; ATM protein; cucurbitacin; Curcuma longa extract; curcumin; DNA; epigallocatechin gallate; genistein; Glycyrrhiza uralensis extract; jaceosidin; lignan; plant extract; plant medicinal product; Polygonum cuspidatum extract; resveratrol; tumor necrosis factor related apoptosis inducing ligand; unclassified drug
EMTREE medical terms: Aglaia; arousal; Artemisia; Artemisia douglasiana; Artemisia princeps; cacao; cancer cell; Cinnamomum; coffee; Curcuma longa; DNA damage; double stranded DNA break; Emilia sonchifolia; Eucalyptus; fruit; Glycyrrhiza uralensis; Gynostemma pentaphyllum; human; inhibition kinetics; intracellular signaling; medicinal plant; modulation; Myristica malabarica; nonhuman; persimmon; plant leaf; Polygonum cuspidatum; Review; rhubarb; sleep; Taiwania cryptomerioides; tea; vegetable
Chemicals and CAS Registry Numbers: apigenin, 520-36-5; curcumin, 458-37-7; DNA, 9007-49-2; epigallocatechin gallate, 989-51-5; genistein, 446-72-0; resveratrol, 501-36-0
ISSN: 0004069X CODEN: AITEASource Type: Journal Original language: English
DOI: 10.1007/s00005-015-0346-xDocument Type: Review
Publisher: Birkhauser Verlag AG
Funding Details
Number; Acronym; Sponsor: 103-2320-B-037-008; MOST; Ministry of Science and Technology of the People's Republic of China