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

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

  • Bioorg Med Chem Lett. 2019 Aug 15;29(16):2189-2196. doi: 10.1016/j.bmcl.2019.06.049.
Jong-Su Kang 1,  June Lee 1,  Le Ba Nam 1,  Ok-Kyung Yoo 1,  Kim-Thanh Pham 1,  Thi-Hoai-Men Duong 1,  Young-Sam Keum 2
Affiliations

Affiliations

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

Figures