Study summary · research use only
Anti-tumor activity of 5-aminoimidazole-4-carboxamide riboside with AMPK-independent cell death in human adult T-cell leukemia/lymphoma
Plain-language summary
Paraphrased from the published abstract below — not a verdict on whether anything works.
This study combined mouse and human cell-line experiments to examine acadesine (AICAR), an AMPK activator, in adult T-cell leukemia/lymphoma (ATL) caused by human T-cell lymphotropic virus type I (HTLV-1). AICAR induced cell death via apoptosis and mitochondrial membrane depolarization in the ATL-related cell lines S1T, MT-1, and MT-2, but not in non-HTLV-1-infected Jurkat cells, without increasing AMPKα phosphorylation. AICAR also increased expression of death receptors DR4 and DR5 and necroptosis-related proteins, and HTLV-1 Tax did not affect AICAR-induced apoptosis. In NOD/SCID/gamma mice, AICAR inhibited growth of human ATL tumor xenografts. The authors suggest these results indicate AICAR induces AMPK-independent cell death in ATL-related cell lines and describe it as a candidate therapeutic agent for ATL.
Abstract
Adult T-cell leukemia/lymphoma (ATL) is an aggressive T cell leukemia/lymphoma caused by human T-cell lymphotropic virus type I (HTLV-1). Acadesine or 5-aminoimidazole-4-carboxamide riboside (AICAR) is an AMP-activated protein kinase (AMPK) activator that was recently shown to have tumor suppressive effects on B cell chronic lymphocytic leukemia, but not ATL. This study evaluated the cytotoxic effects of AICAR on ATL-related cell lines and its anti-tumor activity. Here, we demonstrated that AICAR induced cell death via apoptosis and the mitochondrial membrane depolarization of ATL-related cell lines (S1T, MT-1, and MT-2) but not non-HTLV-1-infected Jurkat cells. However, AICAR did not increase the phosphorylation levels of AMPKα. In addition, AICAR increased the expression of the death receptors (DR) DR4 and DR5, and necroptosis-related proteins including phosphorylated receptor-interacting protein family members and the mixed lineage kinase domain-like protein. Interestingly, HTLV-1 Tax, an HTLV-1-encoded oncogenic factor, did not affect AICAR-induced apoptosis. Furthermore, AICAR inhibited the growth of human ATL tumor xenografts in NOD/SCID/gamma mice in vivo. Together, these results suggest that AICAR induces AMPK-independent cell death in ATL-related cell lines and has anti-tumor activity, indicating that it might be a therapeutic agent for ATL.
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