Possible Interaction: Caffeine and Hydroxyurea

“For a variety of pharmaceutical agents (acetazolamide, mitomycin C, hydroxyurea , 5-fluorouracil), caffeine was shown to enhance the teratogenic effect of the agent.”

“Because caffeine increases the number of growing points, it also partially reversed the inhibition of total DNA synthesis induced by hydroxyurea.”

“Moreover, caffeine , a known ATM/ATR kinase inhibitor, relieved the phosphorylation of cdc2 (Tyr‐15) by hydroxyurea , but not that by lithium.”

“Furthermore, CHK1 hyperphosphorylation induced by caffeine in combination with hydroxyurea is ATR-dependent suggesting that ATR activity is stimulated by caffeine.”

“ Caffeine and HU inhibited US of DNA more intensely in PGA-stimulated cells, and ara-C and ara-C in combination with HU --in unstimulated cells.”

“In addition, rapid killing occurs if caffeine is added to cultures that have been incubated in the presence of hydroxyurea from early G1 and are blocked at the beginning of S, although such cells are killed only slowly on continued incubation in ⩾ 10 mM hydroxyurea alone.”

“Both caffeine and HU are believed to reduce the efficiency of the repair process; caffeine by shortening the time available for repair and HU by reducing the supply of material required for repair.”

“ Caffeine prevented activation of Cds1 and phosphorylation of Chk1, two protein kinases that enforce the S-M checkpoint triggered by hydroxyurea.”

“Chinese hamster ovary (CHO) cells, which are arrested at the G1/S-phase of the cell cycle with hydroxyurea , enter mitosis prematurely when treated with caffeine [Schlegel and Pardee, 1986; Science 233-1264-1266].”

“In the absence of Cdc25, caffeine inhibited cell cycle progression even in the presence of hydroxyurea or phleomycin.”