Emodin and DHA potently increase arsenic trioxide interferon-α–induced cell death of HTLV-I–transformed cells by generation of reactive oxygen species and inhibition of Akt and AP-1

摘要: Adult T-cell leukemia (ATL) is an aggressive lymphoproliferative disease of poor clinical prognosis associated with infection by the human virus type I (HTLV-I). The use arsenic trioxide (As2O3) has been shown to effectively treat acute promyelocytic (APL) greater than 80% patients achieving complete remission. combination and interferon also promising results in treatment ATL. requirement for slow dosage increases time required achieve a pharmacologic active dose major obstacle because median survival ATL about 6 months. In this study we report potent synergistic effect α (As/IFN-α) emodin DHA on cell-cycle arrest cell death HTLV-I–infected cells. Importantly, found that clinically achievable doses allowed reduced concentrations 100-fold while still remaining highly toxic tumor Our data provide rationale combined As/IFN-α refractory conventional therapy.