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Herein, we evaluated the anticancer efficacy of <jats:italic>Abrus<\/jats:italic> agglutinin (AGG), a plant lectin, in oral squamous cell carcinoma. AGG selectively inhibited cell growth, and caused cell cycle arrest and mitochondrial apoptosis through a reactive oxygen species (ROS)\u2010mediated ATM\u2010p73 dependent pathway in FaDu cells. AGG\u2010induced ROS accumulation was identified as the major mechanism regulating apoptosis, DNA damage and DNA\u2010damage response, which were significantly reversed by ROS scavenger N\u2010acetylcysteine (NAC). Moreover, AGG was found to interact with mitochondrial manganese\u2010dependent superoxide dismutase that might inhibit its activity and increase ROS in FaDu cells. In oral cancer p53 is mutated, thus we focused on p73; AGG resulted in p73 upregulation and knock down of p73 caused a decrease in AGG\u2010induced apoptosis. Interestingly, AGG\u2010dependent p73 expression was found to be regulated by ROS, which was reversed by NAC treatment. A reduction in the level of p73 in AGG\u2010treated shATM cells was found to be associated with a decreased apoptosis. Moreover, administration of AGG (50\u2009\u03bcg\/kg body weight) significantly inhibited the growth of FaDu xenografts in athymic nude mice. In immunohistochemical analysis, the xenografts from AGG\u2010treated mice displayed a decrease in PCNA expression and an increase in caspase\u20103 activation as compared to the controls. In conclusion, we established a connection among ROS, ATM and p73 in AGG\u2010induced apoptosis, which might be useful in enhancing the therapeutic targeting of p53 deficient oral squamous cell carcinoma.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mc.22679","type":"journal-article","created":{"date-parts":[[2017,5,24]],"date-time":"2017-05-24T01:00:39Z","timestamp":1495587639000},"page":"2400-2413","source":"Crossref","is-referenced-by-count":28,"title":["<i>Abrus<\/i> agglutinin promotes irreparable DNA damage by triggering ROS generation followed by ATM\u2010p73 mediated apoptosis in oral squamous cell carcinoma"],"prefix":"10.1002","volume":"56","author":[{"given":"Niharika","family":"Sinha","sequence":"first","affiliation":[{"name":"Department of Life Science National Institute of Technology Rourkela India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Prashanta K.","family":"Panda","sequence":"additional","affiliation":[{"name":"Department of Life Science National 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