Cryptophycin 1 cellular levels and effects in vitro using L1210

Cryptophycin 1 is a natural product that was initially isolated from blue-g reen algae which has shown potent broad spectrum antitumor activity in prec linical in vitro and in vivo models. The drug strongly binds to tubulin and disrupts microtubule assembly for more than 24 hours after its removal. We evaluated cell survival, intracellular levels and inhibition of macromolec ular synthesis in L1210 cells following exposure to cryptophycin 1 in vitro . Cell survival was strongly inhibited following drug exposure for either 1 or 4 hours. Intracellular drug levels were minimally affected by temperatu re (4 degrees C vel sus 37 degrees C) or exposure times up to 1 hour. Howev er, extracellular drug concentration in culture media and increasing cell n umbers did affect the concentration of intracellular drug levels in a nearl y proportional manner. The synthesis of DNA and RNA was inhibited less than 5%, while protein synthesis inhibition was near 30%. Thus, none of the mac romolecules were inhibited enough to explain the inhibition of tumor cell g rowth.