Eupafolin suppresses prostate cancer by targeting phosphatidylinositol 3-kinase-mediated Akt signaling

Kangdong Liu; Chanmi Park; Hanyong Chen; Joonsung Hwang; N. R. Thimmegowda; Eun Young Bae; Ki Won Lee; Hong Gyum Kim; Haidan Liu; Nak Kyun Soung; Cong Peng; Jae Hyuk Jang; Kyoon Eon Kim; Jong Seog Ahn; Ann M. Bode; Ziming Dong; Bo Yeon Kim; Zigang Dong

doi:10.1002/mc.22139

Eupafolin suppresses prostate cancer by targeting phosphatidylinositol 3-kinase-mediated Akt signaling

Kangdong Liu, Chanmi Park, Hanyong Chen, Joonsung Hwang, N. R. Thimmegowda, Eun Young Bae, Ki Won Lee, Hong Gyum Kim, Haidan Liu, Nak Kyun Soung, Cong Peng, Jae Hyuk Jang, Kyoon Eon Kim, Jong Seog Ahn, Ann M. Bode, Ziming Dong, Bo Yeon Kim, Zigang Dong

The Hormel Institute

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

25 Scopus citations

Abstract

Phosphatase and tensin homolog (PTEN) loss or mutation consistently activates the phosphatidylinositol 3-kinase (PI3-K)/Akt signaling pathway, which contributes to the progression and invasiveness of prostate cancer. Furthermore, the PTEN/PI3-K/Akt and Ras/MAPK pathways cooperate to promote the epithelial-mesenchymal transition (EMT) and metastasis initiated from prostate stem/progenitor cells. For these reasons, the PTEN/PI3-K/Akt pathway is considered as an attractive target for both chemoprevention and chemotherapy. Herein we report that eupafolin, a natural compound found in common sage, inhibited proliferation of prostate cancer cells. Protein content analysis indicated that phosphorylation of Akt and its downstream kinases was inhibited by eupafolin treatment. Pull-down assay and in vitro kinase assay results indicated that eupafolin could bind with PI3-K and attenuate its kinase activity. Eupafolin also exhibited tumor suppressive effects in vivo in an athymic nude mouse model. Overall, these results suggested that eupafolin exerts antitumor effects by targeting PI3-K.

Original language	English (US)
Pages (from-to)	751-760
Number of pages	10
Journal	Molecular Carcinogenesis
Volume	54
Issue number	9
DOIs	https://doi.org/10.1002/mc.22139
State	Published - Sep 1 2015

Bibliographical note

Publisher Copyright:
© 2014 Wiley Periodicals, Inc..

Keywords

Akt
Chemoprevention
Eupafolin
Phosphatidylinositol 3-kinase
Prostate cancer

UN SDGs

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

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10.1002/mc.22139

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Liu, K., Park, C., Chen, H., Hwang, J., Thimmegowda, N. R., Bae, E. Y., Lee, K. W., Kim, H. G., Liu, H., Soung, N. K., Peng, C., Jang, J. H., Kim, K. E., Ahn, J. S., Bode, A. M., Dong, Z., Kim, B. Y., & Dong, Z. (2015). Eupafolin suppresses prostate cancer by targeting phosphatidylinositol 3-kinase-mediated Akt signaling. Molecular Carcinogenesis, 54(9), 751-760. https://doi.org/10.1002/mc.22139

Liu, K, Park, C, Chen, H, Hwang, J, Thimmegowda, NR, Bae, EY, Lee, KW, Kim, HG, Liu, H, Soung, NK, Peng, C, Jang, JH, Kim, KE, Ahn, JS, Bode, AM, Dong, Z, Kim, BY & Dong, Z 2015, 'Eupafolin suppresses prostate cancer by targeting phosphatidylinositol 3-kinase-mediated Akt signaling', Molecular Carcinogenesis, vol. 54, no. 9, pp. 751-760. https://doi.org/10.1002/mc.22139

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title = "Eupafolin suppresses prostate cancer by targeting phosphatidylinositol 3-kinase-mediated Akt signaling",

abstract = "Phosphatase and tensin homolog (PTEN) loss or mutation consistently activates the phosphatidylinositol 3-kinase (PI3-K)/Akt signaling pathway, which contributes to the progression and invasiveness of prostate cancer. Furthermore, the PTEN/PI3-K/Akt and Ras/MAPK pathways cooperate to promote the epithelial-mesenchymal transition (EMT) and metastasis initiated from prostate stem/progenitor cells. For these reasons, the PTEN/PI3-K/Akt pathway is considered as an attractive target for both chemoprevention and chemotherapy. Herein we report that eupafolin, a natural compound found in common sage, inhibited proliferation of prostate cancer cells. Protein content analysis indicated that phosphorylation of Akt and its downstream kinases was inhibited by eupafolin treatment. Pull-down assay and in vitro kinase assay results indicated that eupafolin could bind with PI3-K and attenuate its kinase activity. Eupafolin also exhibited tumor suppressive effects in vivo in an athymic nude mouse model. Overall, these results suggested that eupafolin exerts antitumor effects by targeting PI3-K.",

keywords = "Akt, Chemoprevention, Eupafolin, Phosphatidylinositol 3-kinase, Prostate cancer",

author = "Kangdong Liu and Chanmi Park and Hanyong Chen and Joonsung Hwang and Thimmegowda, {N. R.} and Bae, {Eun Young} and Lee, {Ki Won} and Kim, {Hong Gyum} and Haidan Liu and Soung, {Nak Kyun} and Cong Peng and Jang, {Jae Hyuk} and Kim, {Kyoon Eon} and Ahn, {Jong Seog} and Bode, {Ann M.} and Ziming Dong and Kim, {Bo Yeon} and Zigang Dong",

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doi = "10.1002/mc.22139",

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AU - Bae, Eun Young

AU - Lee, Ki Won

AU - Kim, Hong Gyum

AU - Liu, Haidan

AU - Soung, Nak Kyun

AU - Peng, Cong

AU - Jang, Jae Hyuk

AU - Kim, Kyoon Eon

AU - Ahn, Jong Seog

AU - Bode, Ann M.

AU - Dong, Ziming

AU - Kim, Bo Yeon

AU - Dong, Zigang

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N2 - Phosphatase and tensin homolog (PTEN) loss or mutation consistently activates the phosphatidylinositol 3-kinase (PI3-K)/Akt signaling pathway, which contributes to the progression and invasiveness of prostate cancer. Furthermore, the PTEN/PI3-K/Akt and Ras/MAPK pathways cooperate to promote the epithelial-mesenchymal transition (EMT) and metastasis initiated from prostate stem/progenitor cells. For these reasons, the PTEN/PI3-K/Akt pathway is considered as an attractive target for both chemoprevention and chemotherapy. Herein we report that eupafolin, a natural compound found in common sage, inhibited proliferation of prostate cancer cells. Protein content analysis indicated that phosphorylation of Akt and its downstream kinases was inhibited by eupafolin treatment. Pull-down assay and in vitro kinase assay results indicated that eupafolin could bind with PI3-K and attenuate its kinase activity. Eupafolin also exhibited tumor suppressive effects in vivo in an athymic nude mouse model. Overall, these results suggested that eupafolin exerts antitumor effects by targeting PI3-K.

AB - Phosphatase and tensin homolog (PTEN) loss or mutation consistently activates the phosphatidylinositol 3-kinase (PI3-K)/Akt signaling pathway, which contributes to the progression and invasiveness of prostate cancer. Furthermore, the PTEN/PI3-K/Akt and Ras/MAPK pathways cooperate to promote the epithelial-mesenchymal transition (EMT) and metastasis initiated from prostate stem/progenitor cells. For these reasons, the PTEN/PI3-K/Akt pathway is considered as an attractive target for both chemoprevention and chemotherapy. Herein we report that eupafolin, a natural compound found in common sage, inhibited proliferation of prostate cancer cells. Protein content analysis indicated that phosphorylation of Akt and its downstream kinases was inhibited by eupafolin treatment. Pull-down assay and in vitro kinase assay results indicated that eupafolin could bind with PI3-K and attenuate its kinase activity. Eupafolin also exhibited tumor suppressive effects in vivo in an athymic nude mouse model. Overall, these results suggested that eupafolin exerts antitumor effects by targeting PI3-K.

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Eupafolin suppresses prostate cancer by targeting phosphatidylinositol 3-kinase-mediated Akt signaling

Abstract

Bibliographical note

Keywords

UN SDGs

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