RNA disruption is associated with response to multiple classes of chemotherapy drugs in tumor cell lines

Narendrula, Rashmi; Mispel-Beyer, Kyle; Guo, Baoqing; Parissenti, Amadeo M.; Pritzker, Laura B.; Pritzker, Ken; Masilamani, Twinkle; Wang, Xiaohui; Lannér, Carita

Previous studies have shown that a variety of apoptosisinducing agents with distinct mechanisms of action (glucocorticoids, okadaic acid, tumor necrosis factor (TNF), dexamethasone, a calcium ionophore and a tricothecene mycotoxin) were able to induce an ordered, apoptosis-associated rRNA degradation in several different cell types, including plant cells and the unicellular organism yeast [11-13, 15-17, 24] . However, this study is the first to report the ability of structurally distinct cytotoxic chemotherapy agents with different mechanisms of action to induce the formation of high molecular weight rRNA degradation fragments (Figs. 1, 2 and 3) , a phenomenon we term "RNA disruption". This suggests that, despite contrasting structures and mechanisms of action, different chemotherapy agents activate a common rRNA degradation mechanism. Moreover, chemotherapy induced RNA disruption was observed across multiple ovarian and breast cancer cell lines, further supporting the widespread nature of this phenomenon (Fig. 3c) .