Broussochalcone a is a novel inhibitor of the orphan nuclear receptor nr4a1 and induces apoptosis in pancreatic cancer cells

Hyo Seon Lee; Soo Hyun Kim; Bo Mi Kim; Stephen Safe; Syng Ook Lee

doi:10.3390/molecules26082316

Broussochalcone a is a novel inhibitor of the orphan nuclear receptor nr4a1 and induces apoptosis in pancreatic cancer cells

Hyo Seon Lee, Soo Hyun Kim, Bo Mi Kim, Stephen Safe, Syng Ook Lee

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

8 Scopus citations

Abstract

The orphan nuclear receptor 4A1 (NR4A1) is overexpressed in pancreatic cancer and exhibits pro-oncogenic activity, and NR4A1 silencing and treatment with its inactivators has been shown to inhibit pancreatic cancer cells and tumor growth. In this study, we identified broussochal-cone A (BCA) as a new NR4A1 inhibitor and demonstrated that BCA inhibits cell growth partly by inducing NR4A1-mediated apoptotic pathways in human pancreatic cancer cells. BCA downreg-ulated specificity protein 1 (Sp1)-mediated expression of an anti-apoptotic protein, survivin, and activated the endoplasmic reticulum (ER) stress-mediated apoptotic pathway. These results suggest that NR4A1 inactivation contributes to the anticancer effects of BCA, and that BCA represents a potential anticancer agent targeting NR4A1 that is overexpressed in many types of human cancers.

Original language	English (US)
Article number	2316
Journal	Molecules
Volume	26
Issue number	8
DOIs	https://doi.org/10.3390/molecules26082316
State	Published - Apr 16 2021

Keywords

Apoptosis
Broussochalcone A
ER stress
NR4A1
Pancreatic cancer
Sp1
Reactive Oxygen Species/metabolism
Nuclear Receptor Subfamily 4, Group A, Member 1/antagonists & inhibitors
Humans
Apoptosis/drug effects
Pancreatic Neoplasms/metabolism
Endoplasmic Reticulum Stress/drug effects
Chalcones/pharmacology
Antineoplastic Agents/pharmacology
Animals
Resorcinols/pharmacology
Cell Line, Tumor

ASJC Scopus subject areas

Drug Discovery
Analytical Chemistry
Chemistry (miscellaneous)
Molecular Medicine
Physical and Theoretical Chemistry
Pharmaceutical Science
Organic Chemistry

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10.3390/molecules26082316

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title = "Broussochalcone a is a novel inhibitor of the orphan nuclear receptor nr4a1 and induces apoptosis in pancreatic cancer cells",

abstract = "The orphan nuclear receptor 4A1 (NR4A1) is overexpressed in pancreatic cancer and exhibits pro-oncogenic activity, and NR4A1 silencing and treatment with its inactivators has been shown to inhibit pancreatic cancer cells and tumor growth. In this study, we identified broussochal-cone A (BCA) as a new NR4A1 inhibitor and demonstrated that BCA inhibits cell growth partly by inducing NR4A1-mediated apoptotic pathways in human pancreatic cancer cells. BCA downreg-ulated specificity protein 1 (Sp1)-mediated expression of an anti-apoptotic protein, survivin, and activated the endoplasmic reticulum (ER) stress-mediated apoptotic pathway. These results suggest that NR4A1 inactivation contributes to the anticancer effects of BCA, and that BCA represents a potential anticancer agent targeting NR4A1 that is overexpressed in many types of human cancers.",

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author = "Lee, {Hyo Seon} and Kim, {Soo Hyun} and Kim, {Bo Mi} and Stephen Safe and Lee, {Syng Ook}",

note = "Funding Information: Funding: This work was supported by the National Research Foundation of Korea [NRF-2020R1A2C1005339]. Publisher Copyright: {\textcopyright} 2021 by the authors. Licensee MDPI, Basel, Switzerland.",

year = "2021",

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language = "English (US)",

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AU - Lee, Hyo Seon

AU - Kim, Soo Hyun

AU - Kim, Bo Mi

AU - Safe, Stephen

AU - Lee, Syng Ook

N1 - Funding Information: Funding: This work was supported by the National Research Foundation of Korea [NRF-2020R1A2C1005339]. Publisher Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland.

PY - 2021/4/16

Y1 - 2021/4/16

N2 - The orphan nuclear receptor 4A1 (NR4A1) is overexpressed in pancreatic cancer and exhibits pro-oncogenic activity, and NR4A1 silencing and treatment with its inactivators has been shown to inhibit pancreatic cancer cells and tumor growth. In this study, we identified broussochal-cone A (BCA) as a new NR4A1 inhibitor and demonstrated that BCA inhibits cell growth partly by inducing NR4A1-mediated apoptotic pathways in human pancreatic cancer cells. BCA downreg-ulated specificity protein 1 (Sp1)-mediated expression of an anti-apoptotic protein, survivin, and activated the endoplasmic reticulum (ER) stress-mediated apoptotic pathway. These results suggest that NR4A1 inactivation contributes to the anticancer effects of BCA, and that BCA represents a potential anticancer agent targeting NR4A1 that is overexpressed in many types of human cancers.

AB - The orphan nuclear receptor 4A1 (NR4A1) is overexpressed in pancreatic cancer and exhibits pro-oncogenic activity, and NR4A1 silencing and treatment with its inactivators has been shown to inhibit pancreatic cancer cells and tumor growth. In this study, we identified broussochal-cone A (BCA) as a new NR4A1 inhibitor and demonstrated that BCA inhibits cell growth partly by inducing NR4A1-mediated apoptotic pathways in human pancreatic cancer cells. BCA downreg-ulated specificity protein 1 (Sp1)-mediated expression of an anti-apoptotic protein, survivin, and activated the endoplasmic reticulum (ER) stress-mediated apoptotic pathway. These results suggest that NR4A1 inactivation contributes to the anticancer effects of BCA, and that BCA represents a potential anticancer agent targeting NR4A1 that is overexpressed in many types of human cancers.

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KW - Chalcones/pharmacology

KW - Antineoplastic Agents/pharmacology

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KW - Resorcinols/pharmacology

KW - Cell Line, Tumor

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Broussochalcone a is a novel inhibitor of the orphan nuclear receptor nr4a1 and induces apoptosis in pancreatic cancer cells

Abstract

Keywords

ASJC Scopus subject areas

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