Preliminary procedural guide for estimating water and sediment yield from roads in forest

CER76-77DBS-RML-LYS21.Prepared for USDA Forest Service, Rocky Mountain Forest and Range Experiment Station.Includes bibliographical references (page 120).November 1976

Activation of the c-Jun N-terminal Kinase/Activating Transcription Factor 3 (ATF3) Pathway Characterizes Effective Arylated Diazeniumdiolate-Based Nitric Oxide-Releasing Anticancer Prodrugs

Improved therapies are needed for nonsmall cell lung cancer. Diazeniumdiolate-based nitric oxide (NO)-releasing prodrugs are a growing class of promising NO-based therapeutics. Recently, we have shown that <i>O</i>²-(2,4-dinitrophenyl) 1-[(4-ethoxycarbonyl)­piperazin-1-yl]­diazen-1-ium-1,2-diolate (JS-K, <b>1</b>) is effective against nonsmall cell lung cancer (NSCLC) cells in culture and in vivo. Here we report mechanistic studies with compound <b>1</b> and its homopiperazine analogue and structural modification of these into more stable prodrugs. Compound <b>1</b> and its homopiperazine analogue were potent cytotoxic agents against NSCLC cells in vitro and in vivo, concomitant with activation of the SAPK/JNK stress pathway and upregulation of its downstream effector ATF3. Apoptosis followed these events. An aryl-substituted analogue, despite extended half-life in the presence of glutathione, did not activate JNK or have antitumor activity. The data suggest that rate of reactivity with glutathione and activation of JNK/ATF3 are determinants of cancer cell killing by these prodrugs