Adult T-cell leukemia/lymphoma (ATLL) is a serious blood malignancy with distinct geographical distribution. ATLL patients have a short survival time because of intrinsic chemoresistance and severe immunosuppression. To introduce a novel treatment, we investigated whether umbelliprenin (UMB), a natural coumarin derivative, could improve the toxicity of arsenic trioxide (ATO) on ATLL cells. To determine the viability of MT-2 cells upon treatment with different concentrations of UMB and ATO, alamarBlue assay was applied. Cell cycle analysis was carried out by propidium iodide staining and the expression of candidate genes was assessed by quantitative reverse transcription-polymerase chain reaction. Our findings revealed that combination of UMB and ATO induced considerable cytotoxic effects on ATLL cells. Flow cytometry analysis indicated accumulation of MT-2 cells in the sub G1 phase of the cell cycle after combinatorial treatment. In addition, significant downregulation in BMI-1, CD44, c-MYC, and nuclear factor-κB (REL-A) expression was observed after UMB +ATO administration. Agents with low side effects are potential candidates for novel cancer treatments. We demonstrated, for the first time, that combination of UMB and ATO might be regarded as an effective regimen for ATLL treatment

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