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

Jong Su Kang; June Lee; Le Ba Nam; Ok Kyung Yoo; Kim Thanh Pham; Thi Hoai Men Duong; Young Sam Keum

doi:10.1016/j.bmcl.2019.06.049

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

Jong Su Kang
, June Lee
, Le Ba Nam
, Ok Kyung Yoo
, Kim Thanh Pham
, Thi Hoai Men Duong
, Young Sam Keum

Department of Pharmacy

Dongguk University

Research output: Contribution to journal › Article › peer-review

17 Scopus citations

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.

Original language	English
Pages (from-to)	2189-2196
Number of pages	8
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	29
Issue number	16
DOIs	https://doi.org/10.1016/j.bmcl.2019.06.049
State	Published - 15 Aug 2019

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

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

Access to Document

10.1016/j.bmcl.2019.06.049

Cite this

@article{9bf879e5776b46f0b05a3c30bb4c6c84,

title = "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.",

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

author = "Kang, \{Jong Su\} and June Lee and Nam, \{Le Ba\} and Yoo, \{Ok Kyung\} and Pham, \{Kim Thanh\} and Duong, \{Thi Hoai Men\} and Keum, \{Young Sam\}",

note = "Publisher Copyright: {\textcopyright} 2019 Elsevier Ltd",

year = "2019",

month = aug,

day = "15",

doi = "10.1016/j.bmcl.2019.06.049",

language = "English",

volume = "29",

pages = "2189--2196",

journal = "Bioorganic and Medicinal Chemistry Letters",

issn = "0960-894X",

publisher = "Elsevier Ltd",

number = "16",

}

TY - JOUR

T1 - Homoharringtonine stabilizes secondary structure of guanine-rich sequence existing in the 5′-untranslated region of Nrf2

AU - Kang, Jong Su

AU - Lee, June

AU - Nam, Le Ba

AU - Yoo, Ok Kyung

AU - Pham, Kim Thanh

AU - Duong, Thi Hoai Men

AU - Keum, Young Sam

PY - 2019/8/15

Y1 - 2019/8/15

N2 - 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.

AB - 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.

KW - 5′-Untranslated region (5′-UTR)

KW - Antioxidant response element (ARE)

KW - Homoharringtonine (HHT)

KW - NF-E2-related factor 2 (NRF2)

UR - https://www.scopus.com/pages/publications/85068094550

U2 - 10.1016/j.bmcl.2019.06.049

DO - 10.1016/j.bmcl.2019.06.049

M3 - Article

C2 - 31270017

AN - SCOPUS:85068094550

SN - 0960-894X

VL - 29

SP - 2189

EP - 2196

JO - Bioorganic and Medicinal Chemistry Letters

JF - Bioorganic and Medicinal Chemistry Letters

IS - 16

ER -

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

Abstract

UN SDGs

Keywords

Access to Document

Other files and links

Fingerprint

Cite this