Tamoxifen enhances romidepsin-induced apoptosis in T-cell malignant cells via activation of FOXO1 signaling pathway

Abstract

Although romidepsin as monotherapy appears to be useful for treating T-cell lymphoma, combined chemotherapy with other therapeutic agents is required for improvement of the treatment outcome. To establish safer and more effective regimens, systematic screening was conducted to identify suitable drugs to be used in combination with romidepsin for T-cell malignancies, and the underlying molecular mechanisms were examined. The most effective agent was tamoxifen. The combination of romidepsin and tamoxifen had a significant synergistic effect in inducing apoptosis. The growth-inhibitory effects of the combined treatment were reversed by α-tocopherol. FOXO1 expression was greatly upregulated in MOLT-4 cells treated with romidepsin plus tamoxifen. Knockdown of FOXO1 expression by siRNA significantly reduced the cell death induced by romidepsin plus tamoxifen. The combination of romidepsin and tamoxifen might be considered for the treatment of T-cell lymphoma patients.

Keywords:

• T-cell lymphoma
• romidepsin
• tamoxifen
• FOXO1
• apoptosis
• lipid peroxidation

Disclosure statement

Junji Suzumiya has received research funding from Celgene.

Additional information

Funding

This study was supported in part by the SUIGAN project, Shimane University, Japan.