To predict the clinical usefulness of
DA-125, a newly developed
doxorubicin analog, we compared its antitumor activity against 20 different human
cancer cell lines with that of
doxorubicin using the MTT in vitro chemosensitivity test. We also measured and compared the cellular uptake of this
drug and
doxorubicin in two
cancer cell lines and their
doxorubicin-resistant sublines. In the MTT test,
DA-125 showed lower IC50 values than
doxorubicin for 14 of 20 cell lines.
DA-125 was more potent than
doxorubicin for
hepatocellular cancer cells with high mdr 1 expression. Among
cancer cells from the stomach and colon,
DA-125 was more potent than
doxorubicin in 12 of 14 cell lines. We also investigated the cross-resistance of this
drug with
doxorubicin using four
doxorubicin-resistant
cancer cell sublines. Except in one cell line, there was very low cross-resistance. Cellular
drug-uptake experiments were performed for two
gastric cancer cell lines and their
doxorubicin-resistant sublines. In this experiment,
DA-125 was found to be very rapidly and completely converted to its active metabolite, M1, in the
culture media. After this conversion, M1 was incorporated into these
cancer cells more rapidly and reached higher intracellular concentrations than
doxorubicin, suggesting that
DA-125 (as M1) could achieve earlier and higher levels of intracellular accumulation than
doxorubicin in its target tissues from the bloodstream. As a possible alternative
antineoplastic agent to
doxorubicin,
DA-125 awaits further evaluation for its antitumor activity and toxicity.