A novel 2-pyrone derivative, BHP, impedes oncogenic KRAS-driven malignant progression in breast cancer

Rae Kwon Kim, Yongjoon Suh, Eun Jung Lim, Ki Chun Yoo, Ga Haeng Lee, Yan Hong Cui, Arang Son, Eunji Hwang, Nizam Uddin, Joo Mi Yi, Seok-Gu Kang, Su Jae Lee

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Elevated KRAS expression has been frequently associated with cancer progression including breast cancer; however, therapeutic approaches targeting KRAS have been widely unsuccessful and KRAS mutant cancers remain unsolved problem in cancer therapy. In this study, we found that a new 2-pyrone derivative, 5-bromo-3-(3-hydroxyprop-1-ynyl)-2H-pyran-2-one (BHP) can block KRAS-driven breast cancer progression. Importantly, treatment with BHP effectively suppressed the migratory and invasive properties along with epithelial-mesenchymal transition (EMT) in MDA-MB231 breast cancer cells that carry oncogenic KRAS and mesenchymal malignant phenotypes. In parallel, BHP also sensitized the cells to anticancer treatment. Consistently, forced-expression of oncogenic KRAS bestowed the migratory and invasive properties, mesenchymal transition and resistance to anticancer treatment into normal human mammalian breast cells MCF10A and relatively non-malignant MCF7 and SK-BR3 breast cancer cells; however, treatment with BHP blocked those KRAS-induced malignant phenotypes. Notably, BHP interfered the interaction of KRAS with Raf-1 in concentration-dependent manner, thereby blocking the downstream effectors of KRAS signaling that is PI3K/AKT and ERK. Taken together, our findings indicate that the BHP, an α-pyrone derivative, suppresses malignant breast cancer progression by targeting of oncogenic KRAS signaling pathways.

Original languageEnglish
Pages (from-to)49-57
Number of pages9
JournalCancer Letters
Volume337
Issue number1
DOIs
Publication statusPublished - 2013 Aug 28

Fingerprint

Breast Neoplasms
Pyrones
Phenotype
Neoplasms
Epithelial-Mesenchymal Transition
Phosphatidylinositol 3-Kinases
Breast
2-pyrone
Therapeutics

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Kim, R. K., Suh, Y., Lim, E. J., Yoo, K. C., Lee, G. H., Cui, Y. H., ... Lee, S. J. (2013). A novel 2-pyrone derivative, BHP, impedes oncogenic KRAS-driven malignant progression in breast cancer. Cancer Letters, 337(1), 49-57. https://doi.org/10.1016/j.canlet.2013.05.023
Kim, Rae Kwon ; Suh, Yongjoon ; Lim, Eun Jung ; Yoo, Ki Chun ; Lee, Ga Haeng ; Cui, Yan Hong ; Son, Arang ; Hwang, Eunji ; Uddin, Nizam ; Yi, Joo Mi ; Kang, Seok-Gu ; Lee, Su Jae. / A novel 2-pyrone derivative, BHP, impedes oncogenic KRAS-driven malignant progression in breast cancer. In: Cancer Letters. 2013 ; Vol. 337, No. 1. pp. 49-57.
@article{8ec8963e27004dbf8fb76c0bc2d225f2,
title = "A novel 2-pyrone derivative, BHP, impedes oncogenic KRAS-driven malignant progression in breast cancer",
abstract = "Elevated KRAS expression has been frequently associated with cancer progression including breast cancer; however, therapeutic approaches targeting KRAS have been widely unsuccessful and KRAS mutant cancers remain unsolved problem in cancer therapy. In this study, we found that a new 2-pyrone derivative, 5-bromo-3-(3-hydroxyprop-1-ynyl)-2H-pyran-2-one (BHP) can block KRAS-driven breast cancer progression. Importantly, treatment with BHP effectively suppressed the migratory and invasive properties along with epithelial-mesenchymal transition (EMT) in MDA-MB231 breast cancer cells that carry oncogenic KRAS and mesenchymal malignant phenotypes. In parallel, BHP also sensitized the cells to anticancer treatment. Consistently, forced-expression of oncogenic KRAS bestowed the migratory and invasive properties, mesenchymal transition and resistance to anticancer treatment into normal human mammalian breast cells MCF10A and relatively non-malignant MCF7 and SK-BR3 breast cancer cells; however, treatment with BHP blocked those KRAS-induced malignant phenotypes. Notably, BHP interfered the interaction of KRAS with Raf-1 in concentration-dependent manner, thereby blocking the downstream effectors of KRAS signaling that is PI3K/AKT and ERK. Taken together, our findings indicate that the BHP, an α-pyrone derivative, suppresses malignant breast cancer progression by targeting of oncogenic KRAS signaling pathways.",
author = "Kim, {Rae Kwon} and Yongjoon Suh and Lim, {Eun Jung} and Yoo, {Ki Chun} and Lee, {Ga Haeng} and Cui, {Yan Hong} and Arang Son and Eunji Hwang and Nizam Uddin and Yi, {Joo Mi} and Seok-Gu Kang and Lee, {Su Jae}",
year = "2013",
month = "8",
day = "28",
doi = "10.1016/j.canlet.2013.05.023",
language = "English",
volume = "337",
pages = "49--57",
journal = "Cancer Letters",
issn = "0304-3835",
publisher = "Elsevier Ireland Ltd",
number = "1",

}

Kim, RK, Suh, Y, Lim, EJ, Yoo, KC, Lee, GH, Cui, YH, Son, A, Hwang, E, Uddin, N, Yi, JM, Kang, S-G & Lee, SJ 2013, 'A novel 2-pyrone derivative, BHP, impedes oncogenic KRAS-driven malignant progression in breast cancer', Cancer Letters, vol. 337, no. 1, pp. 49-57. https://doi.org/10.1016/j.canlet.2013.05.023

A novel 2-pyrone derivative, BHP, impedes oncogenic KRAS-driven malignant progression in breast cancer. / Kim, Rae Kwon; Suh, Yongjoon; Lim, Eun Jung; Yoo, Ki Chun; Lee, Ga Haeng; Cui, Yan Hong; Son, Arang; Hwang, Eunji; Uddin, Nizam; Yi, Joo Mi; Kang, Seok-Gu; Lee, Su Jae.

In: Cancer Letters, Vol. 337, No. 1, 28.08.2013, p. 49-57.

Research output: Contribution to journalArticle

TY - JOUR

T1 - A novel 2-pyrone derivative, BHP, impedes oncogenic KRAS-driven malignant progression in breast cancer

AU - Kim, Rae Kwon

AU - Suh, Yongjoon

AU - Lim, Eun Jung

AU - Yoo, Ki Chun

AU - Lee, Ga Haeng

AU - Cui, Yan Hong

AU - Son, Arang

AU - Hwang, Eunji

AU - Uddin, Nizam

AU - Yi, Joo Mi

AU - Kang, Seok-Gu

AU - Lee, Su Jae

PY - 2013/8/28

Y1 - 2013/8/28

N2 - Elevated KRAS expression has been frequently associated with cancer progression including breast cancer; however, therapeutic approaches targeting KRAS have been widely unsuccessful and KRAS mutant cancers remain unsolved problem in cancer therapy. In this study, we found that a new 2-pyrone derivative, 5-bromo-3-(3-hydroxyprop-1-ynyl)-2H-pyran-2-one (BHP) can block KRAS-driven breast cancer progression. Importantly, treatment with BHP effectively suppressed the migratory and invasive properties along with epithelial-mesenchymal transition (EMT) in MDA-MB231 breast cancer cells that carry oncogenic KRAS and mesenchymal malignant phenotypes. In parallel, BHP also sensitized the cells to anticancer treatment. Consistently, forced-expression of oncogenic KRAS bestowed the migratory and invasive properties, mesenchymal transition and resistance to anticancer treatment into normal human mammalian breast cells MCF10A and relatively non-malignant MCF7 and SK-BR3 breast cancer cells; however, treatment with BHP blocked those KRAS-induced malignant phenotypes. Notably, BHP interfered the interaction of KRAS with Raf-1 in concentration-dependent manner, thereby blocking the downstream effectors of KRAS signaling that is PI3K/AKT and ERK. Taken together, our findings indicate that the BHP, an α-pyrone derivative, suppresses malignant breast cancer progression by targeting of oncogenic KRAS signaling pathways.

AB - Elevated KRAS expression has been frequently associated with cancer progression including breast cancer; however, therapeutic approaches targeting KRAS have been widely unsuccessful and KRAS mutant cancers remain unsolved problem in cancer therapy. In this study, we found that a new 2-pyrone derivative, 5-bromo-3-(3-hydroxyprop-1-ynyl)-2H-pyran-2-one (BHP) can block KRAS-driven breast cancer progression. Importantly, treatment with BHP effectively suppressed the migratory and invasive properties along with epithelial-mesenchymal transition (EMT) in MDA-MB231 breast cancer cells that carry oncogenic KRAS and mesenchymal malignant phenotypes. In parallel, BHP also sensitized the cells to anticancer treatment. Consistently, forced-expression of oncogenic KRAS bestowed the migratory and invasive properties, mesenchymal transition and resistance to anticancer treatment into normal human mammalian breast cells MCF10A and relatively non-malignant MCF7 and SK-BR3 breast cancer cells; however, treatment with BHP blocked those KRAS-induced malignant phenotypes. Notably, BHP interfered the interaction of KRAS with Raf-1 in concentration-dependent manner, thereby blocking the downstream effectors of KRAS signaling that is PI3K/AKT and ERK. Taken together, our findings indicate that the BHP, an α-pyrone derivative, suppresses malignant breast cancer progression by targeting of oncogenic KRAS signaling pathways.

UR - http://www.scopus.com/inward/record.url?scp=84880035860&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84880035860&partnerID=8YFLogxK

U2 - 10.1016/j.canlet.2013.05.023

DO - 10.1016/j.canlet.2013.05.023

M3 - Article

VL - 337

SP - 49

EP - 57

JO - Cancer Letters

JF - Cancer Letters

SN - 0304-3835

IS - 1

ER -