Possible Interaction: Caffeine and Ammonium Tetrathiomolybdate

“ Caffeine has also been reported to inhibit ATM and ATR kinases which leads to the disruption of multiple DNA damage-responsive cell cycle checkpoints and greatly sensitizes tumor cells to antitumor agents which induce genotoxic stress.”

“ Caffeine abrogated this amplification in both ATM (ataxia telangiectasia, mutated)‐ and ATR (ATM and Rad3‐related)‐defective cells, indicating a complementary role for these DNA‐damage‐responsive kinases in promoting centrosome amplification.”

“Inhibition of ATM and ATR with caffeine or specific neutralizing antibodies, or upregulation of Cdk2 or Cdc7, promoted rapid and synchronous origin firing; conversely, inhibition of Cdc25A slowed DNA replication.”

“ Caffeine , as a nonspecific inhibitor of ATM and ATR, abolishes multi-checkpoint responses and sensitizes cells to radiation-induced killing.”

“ Caffeine was eventually shown to inhibit the DNA damage response proteins ATR and ATM , but the required concentrations could not be achieved in patients.”

“2) ATM inhibition by caffeine prevents G2 cell arrest and in p53-positive cells MOLT-4 delays the onset of mitoxantrone-induced cell death.”

“Inhibition of ATM with caffeine , KU-55933, or siRNA or inhibition of the MEK/ERK pathway can block the LDR-induced NF-kappaB activation and eliminate the LDR-induced survival advantage.”

“Moreover, inhibition of ATM and ATR by caffeine suppressed JCV production.”

“In contrast, inhibition of ATM and ATR by caffeine had the inverse effect of blocking IR-, but not chromium-induced p53 stabilization and activation.”

“However, when ATM is inhibited by caffeine , ATR activation is markedly enhanced.”