Dimethyl Fumarate Induces Apoptosis via Inhibiting NF-κB and STAT3 Signaling in Adult T-cell Leukemia/Lymphoma Cells.

Abstract

BACKGROUND/AIM:

Adult T-cell leukemia (ATL) is a peripheral T lymphocytic malignancy caused by human T-cell leukemia virus type 1 (HTLV-1) infection. Despite treatment that includes novel agents that have been developed, most of ATL patients relapse and acquire multidrug resistance. As a result, the creation of newer agents is critical. Dimethyl fumarate (DMF) has several effects in cancer cells, including cell signaling, proliferation and cell death. However, its antitumor effects on ATL cells remain unknown. In this study, we looked at DMF's antitumor effects on ATL cells.

MATERIALS AND METHODS:

We examined the effects of DMF on proliferation and apoptosis using the trypan blue exclusion assay and annexin V/propidium iodide staining in HTLV-1-infected and transformed T-cell lines, MT-1 and MT-2 cells. We also evaluated the effects of DMF on the nuclear factor-kappa B (NF-κB) and signal transducers and activators of transcription 3 (STAT3) signaling pathways and anti-apoptotic proteins by immunoblotting.

RESULTS:

DMF inhibited proliferation and induced apoptosis in MT-1 and MT-2 cells by activating poly ADP-ribose polymerase (PARP). Furthermore, DMF inhibited the constitutive activation of both canonical and non-canonical NF-κB pathways in MT-2 cells and the non-canonical NF-κB pathway in MT-1 cells. DMF also inhibited the constitutive tyrosine phosphorylation of STAT3 and the expression of anti-apoptotic proteins, c-IAP2 and survivin in both cells.

CONCLUSION:

These results indicate that DMF inhibits proliferation and induces apoptosis in HTLV-1-infected and transformed T-cells by suppressing NF-κB and STAT3 signaling pathways. DMF should be investigated further as a novel agent for ATL.

• Authors: Takahiro Maeta, Tsuyoshi Sato, Kazuya Asano, Shigeki Ito
• Journal: Anticancer research (Anticancer Res) Vol. 42 Issue 5 Pg. 2301-2309 (May 2022) ISSN: 1791-7530 [Electronic] Greece
• PMID: 35489748 (Publication Type: Journal Article)
• Copyright: Copyright © 2022 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Chemical References

• NF-kappa B
• STAT3 Transcription Factor
• STAT3 protein, human
• Dimethyl Fumarate

Topics

• Adult
• Apoptosis
• Dimethyl Fumarate (pharmacology, therapeutic use)
• Human T-lymphotropic virus 1 (metabolism)
• Humans
• Leukemia-Lymphoma, Adult T-Cell (drug therapy)
• Lymphoma
• NF-kappa B (metabolism)
• STAT3 Transcription Factor (metabolism)
• Signal Transduction