Format

Send to

Choose Destination
Bioorg Med Chem Lett. 2019 Jun 27. pii: S0960-894X(19)30431-7. doi: 10.1016/j.bmcl.2019.06.049. [Epub ahead of print]

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

Author information

1
College of Pharmacy and Integrated Research Institute for Drug Development, Dongguk University, 32 Dongguk-ro, Goyang, Gyeonggi-do 10326, South Korea.
2
College of Pharmacy and Integrated Research Institute for Drug Development, Dongguk University, 32 Dongguk-ro, Goyang, Gyeonggi-do 10326, South Korea. Electronic address: keum03@dongguk.edu.

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.

KEYWORDS:

5′-Untranslated region (5′-UTR); Antioxidant response element (ARE); Homoharringtonine (HHT); NF-E2-related factor 2 (NRF2)

PMID:
31270017
DOI:
10.1016/j.bmcl.2019.06.049

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center