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

15 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

Keywords

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

UN SDGs

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

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10.1016/j.bmcl.2019.06.049

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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",

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journal = "Bioorganic and Medicinal Chemistry Letters",

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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 - http://www.scopus.com/inward/record.url?scp=85068094550&partnerID=8YFLogxK

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

Keywords

UN SDGs

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