Anticancer activity of methoxymorpholinyl doxorubicin (PNU 152243) on human hepatocellular carcinoma

Methoxymorpholinyl doxorubicin (PNU 152243) is a morpholinyl analog possessing a methoxymorpholinyl group at the 3′ position of the sugar moiety, which, compared with doxorubicin, appears to be less cardiotoxic and more cytotoxic against multidrug-resistant tumor cells. In this study, we report the anticancer activity of PNU 152243 on human hepatocellular carcinoma (HCC) in vitro and in vivo. The average IC₅₀ value of PNU was 0.08 μM. In contrast, the average IC₅₀ values of adriamycin (ADM), 4′-epidoxorubicin (EDR), mitomycin C (MMC), cisplatin and vepesid (VP-16) were 0.96, 0.74, 2.81, 7.27 and 26.66 μM, respectively. PNU 152243 was 13.7, 10.6, 40.1, 103.8 and 380.8 times more potent than ADM, EDR, MMC, cisplatin and VP-16 against HCC in vitro. In nude mice, the T/C (%) were 43.8 at the dose of 25 μg/kg and 41.2 at the dose of 50 μg/kg on BEL-7402 xenograft, the T/C (%) were 41.7 at the dose of 25 μg/kg and 54.6 at the dose of 50 μg/kg on Zip-177 xenograft. The results showed that PNU 152243 had growth inhibition of HCC in vitro and in vivo and may be useful in HCC chemotherapy.