Coumestrol suppresses hypoxia inducible factor 1α by inhibiting ROS mediated sphingosine kinase 1 in hypoxic PC-3 prostate cancer cells

Sung Yun Cho; Sunmi Cho; Eunkyung Park; Bonglee Kim; Eun Jung Sohn; Bumsuk Oh; Eun Ok Lee; Hyo Jeong Lee; Sung Hoon Kim

doi:10.1016/j.bmcl.2014.03.084

Coumestrol suppresses hypoxia inducible factor 1α by inhibiting ROS mediated sphingosine kinase 1 in hypoxic PC-3 prostate cancer cells

Sung Yun Cho, Sunmi Cho, Eunkyung Park, Bonglee Kim, Eun Jung Sohn, Bumsuk Oh, Eun Ok Lee, Hyo Jeong Lee, Sung Hoon Kim

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

34 Citations (Scopus)

Abstract

Among many signals to regulate hypoxia inducible factor 1α (HIF-1α), sphingosine kinase 1 (SPHK1) is also involved in various biological activities such as cell growth, survival, invasion, angiogenesis, and carcinogenesis. Thus, in the present study, molecular mechanisms of coumestrol were investigated on the SPHK1 and HIF-1α signaling pathway in hypoxic PC-3 prostate cancer cells. Coumestrol significantly suppressed SPHK1 activity and accumulation of HIF-1α in a time- and concentration-dependent manner in hypoxic PC-3 cells. In addition, coumestrol inhibited the phosphorylation status of AKT and glycogen synthase kinase-3β (GSK 3β) signaling involved in cancer metabolism. Furthermore, SPHK1 siRNA transfection, sphigosine kinase inhibitor (SKI), reactive oxygen species (ROS) enhanced the inhibitory effect of coumestrol on the accumulation of HIF-1α and the expression of pAKT and pGSK 3β in hypoxic PC-3 cells by combination index. Overall, our findings suggest that coumestrol suppresses the accumulation of HIF-1α via suppression of SPHK1 pathway in hypoxic PC-3 cells.

Original language	English
Pages (from-to)	2560-2564
Number of pages	5
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	24
Issue number	11
DOIs	https://doi.org/10.1016/j.bmcl.2014.03.084
Publication status	Published - 1 Jun 2014

Bibliographical note

Funding Information:
This work was supported by the Korea Science and Engineering Foundation (KOSEF) Grant funded by the Korea Government (MEST) (No. 2012-0005755 ). The authors declare no competing interests.

Keywords

Coumestrol
Hypoxia inducible factor 1α
Reactive oxygen species

UN SDGs

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

Access to Document

10.1016/j.bmcl.2014.03.084

Cite this

@article{4f6249b43eb648e8822cd168f1ee2c62,

title = "Coumestrol suppresses hypoxia inducible factor 1α by inhibiting ROS mediated sphingosine kinase 1 in hypoxic PC-3 prostate cancer cells",

abstract = "Among many signals to regulate hypoxia inducible factor 1α (HIF-1α), sphingosine kinase 1 (SPHK1) is also involved in various biological activities such as cell growth, survival, invasion, angiogenesis, and carcinogenesis. Thus, in the present study, molecular mechanisms of coumestrol were investigated on the SPHK1 and HIF-1α signaling pathway in hypoxic PC-3 prostate cancer cells. Coumestrol significantly suppressed SPHK1 activity and accumulation of HIF-1α in a time- and concentration-dependent manner in hypoxic PC-3 cells. In addition, coumestrol inhibited the phosphorylation status of AKT and glycogen synthase kinase-3β (GSK 3β) signaling involved in cancer metabolism. Furthermore, SPHK1 siRNA transfection, sphigosine kinase inhibitor (SKI), reactive oxygen species (ROS) enhanced the inhibitory effect of coumestrol on the accumulation of HIF-1α and the expression of pAKT and pGSK 3β in hypoxic PC-3 cells by combination index. Overall, our findings suggest that coumestrol suppresses the accumulation of HIF-1α via suppression of SPHK1 pathway in hypoxic PC-3 cells.",

keywords = "Coumestrol, Hypoxia inducible factor 1α, Reactive oxygen species",

author = "Cho, {Sung Yun} and Sunmi Cho and Eunkyung Park and Bonglee Kim and Sohn, {Eun Jung} and Bumsuk Oh and Lee, {Eun Ok} and Lee, {Hyo Jeong} and Kim, {Sung Hoon}",

note = "Funding Information: This work was supported by the Korea Science and Engineering Foundation (KOSEF) Grant funded by the Korea Government (MEST) (No. 2012-0005755 ). The authors declare no competing interests. ",

year = "2014",

month = jun,

day = "1",

doi = "10.1016/j.bmcl.2014.03.084",

language = "English",

volume = "24",

pages = "2560--2564",

journal = "Bioorganic and Medicinal Chemistry Letters",

issn = "0960-894X",

publisher = "Elsevier Ltd.",

number = "11",

}

TY - JOUR

T1 - Coumestrol suppresses hypoxia inducible factor 1α by inhibiting ROS mediated sphingosine kinase 1 in hypoxic PC-3 prostate cancer cells

AU - Cho, Sung Yun

AU - Cho, Sunmi

AU - Park, Eunkyung

AU - Kim, Bonglee

AU - Sohn, Eun Jung

AU - Oh, Bumsuk

AU - Lee, Eun Ok

AU - Lee, Hyo Jeong

AU - Kim, Sung Hoon

N1 - Funding Information: This work was supported by the Korea Science and Engineering Foundation (KOSEF) Grant funded by the Korea Government (MEST) (No. 2012-0005755 ). The authors declare no competing interests.

PY - 2014/6/1

Y1 - 2014/6/1

N2 - Among many signals to regulate hypoxia inducible factor 1α (HIF-1α), sphingosine kinase 1 (SPHK1) is also involved in various biological activities such as cell growth, survival, invasion, angiogenesis, and carcinogenesis. Thus, in the present study, molecular mechanisms of coumestrol were investigated on the SPHK1 and HIF-1α signaling pathway in hypoxic PC-3 prostate cancer cells. Coumestrol significantly suppressed SPHK1 activity and accumulation of HIF-1α in a time- and concentration-dependent manner in hypoxic PC-3 cells. In addition, coumestrol inhibited the phosphorylation status of AKT and glycogen synthase kinase-3β (GSK 3β) signaling involved in cancer metabolism. Furthermore, SPHK1 siRNA transfection, sphigosine kinase inhibitor (SKI), reactive oxygen species (ROS) enhanced the inhibitory effect of coumestrol on the accumulation of HIF-1α and the expression of pAKT and pGSK 3β in hypoxic PC-3 cells by combination index. Overall, our findings suggest that coumestrol suppresses the accumulation of HIF-1α via suppression of SPHK1 pathway in hypoxic PC-3 cells.

AB - Among many signals to regulate hypoxia inducible factor 1α (HIF-1α), sphingosine kinase 1 (SPHK1) is also involved in various biological activities such as cell growth, survival, invasion, angiogenesis, and carcinogenesis. Thus, in the present study, molecular mechanisms of coumestrol were investigated on the SPHK1 and HIF-1α signaling pathway in hypoxic PC-3 prostate cancer cells. Coumestrol significantly suppressed SPHK1 activity and accumulation of HIF-1α in a time- and concentration-dependent manner in hypoxic PC-3 cells. In addition, coumestrol inhibited the phosphorylation status of AKT and glycogen synthase kinase-3β (GSK 3β) signaling involved in cancer metabolism. Furthermore, SPHK1 siRNA transfection, sphigosine kinase inhibitor (SKI), reactive oxygen species (ROS) enhanced the inhibitory effect of coumestrol on the accumulation of HIF-1α and the expression of pAKT and pGSK 3β in hypoxic PC-3 cells by combination index. Overall, our findings suggest that coumestrol suppresses the accumulation of HIF-1α via suppression of SPHK1 pathway in hypoxic PC-3 cells.

KW - Coumestrol

KW - Hypoxia inducible factor 1α

KW - Reactive oxygen species

UR - http://www.scopus.com/inward/record.url?scp=84899916910&partnerID=8YFLogxK

U2 - 10.1016/j.bmcl.2014.03.084

DO - 10.1016/j.bmcl.2014.03.084

M3 - Article

C2 - 24768446

AN - SCOPUS:84899916910

SN - 0960-894X

VL - 24

SP - 2560

EP - 2564

JO - Bioorganic and Medicinal Chemistry Letters

JF - Bioorganic and Medicinal Chemistry Letters

IS - 11

ER -

Coumestrol suppresses hypoxia inducible factor 1α by inhibiting ROS mediated sphingosine kinase 1 in hypoxic PC-3 prostate cancer cells

Abstract

Bibliographical note

Keywords

UN SDGs

Access to Document

Other files and links

Fingerprint

Cite this