Liblomycin (
NK313) is a novel derivative of
bleomycin (BLM) and
peplomycin (PEP). The cell kill kinetics of
NK313 on rat
ascites hepatoma AH66 were compared with those of PEP.
NK313 induced intracellular DNA cleavage and arrested cell cycle progression at the G2 phase similarly to PEP. The cytocidal effect of
NK313, however, was found to be different from that of PEP as described below: 1) The dose-survival curve for cells exposed to PEP for 1 hour was upward concave, whereas in case of
NK313, the survival curve was linear. PEP was more effective to AH66 than
NK313 at lower concentration, but at higher concentration,
NK313 was much more effective. 2) The time-survival curve for cells treated with either
NK313 or PEP was biphasic.
NK313, however, did not induce temporary resistance of AH66 cells to
NK313, while PEP induced resistance to PEP. 3)
NK313 was effective against the cells which became temporarily resistant to PEP by the treatment of PEP. These differences suggest that
NK313 might be of value to treat PEP-insensitive
tumor cells.