Homoharringtonine stabilizes secondary structure of guanine-rich sequence existing in the 5'-untranslated region of Nrf2.

Abstract

Homoharringtonine, known as omacetaxine mepesuccinate, is a pharmaceutical drug substance approved for treatment of chronic myeloid leukemia. Here, we report that homoharringtonine (HHT) is a novel chemical inhibitor of NRF2. HHT significantly suppressed NRF2 and ARE-dependent gene expression in human lung carcinoma A549 cells. HHT stabilized secondary structure of guanine-rich sequence existing in the 5'-untranslated region (5'-UTR) of Nrf2 and sensitized A549 cells to etoposide-induced apoptosis. To the best of our knowledge, HHT is the first type of transcriptional inhibitor of Nrf2 that stabilizes guanine-rich sequence existing in the 5'-UTR. Our study also provides a novel mechanism of action underlying how HHT exerts anti-carcinogenic effects in cancer cells.

• Authors: Jong-Su Kang, June Lee, Le Ba Nam, Ok-Kyung Yoo, Kim-Thanh Pham, Thi-Hoai-Men Duong, Young-Sam Keum
• Journal: Bioorganic & medicinal chemistry letters (Bioorg Med Chem Lett) Vol. 29 Issue 16 Pg. 2189-2196 (08 15 2019) ISSN: 1464-3405 [Electronic] England
• PMID: 31270017 (Publication Type: Letter, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2019 Elsevier Ltd. All rights reserved.

Chemical References

• 5' Untranslated Regions
• Antineoplastic Agents, Phytogenic
• NF-E2-Related Factor 2
• Guanine
• Homoharringtonine

Topics

• 5' Untranslated Regions (genetics)
• Antineoplastic Agents, Phytogenic (pharmacology, therapeutic use)
• Guanine (chemistry)
• Homoharringtonine (pharmacology, therapeutic use)
• Humans
• NF-E2-Related Factor 2 (genetics)