Repression of oncogenic cap-mediated translation by 4Ei-10 diminishes proliferation, enhances chemosensitivity and alters expression of malignancy-related proteins in mesothelioma

Zeeshan Ahmad; Blake A. Jacobson; Mitchell W. McDonald; Nicolas Vattendahl Vidal; Gabriel Vattendahl Vidal; Sierra Chen; Maxwell Dillenburg; Aniekan M. Okon; Manish R. Patel; Carston R. Wagner; Robert A. Kratzke

doi:10.1007/s00280-020-04029-9

Repression of oncogenic cap-mediated translation by 4Ei-10 diminishes proliferation, enhances chemosensitivity and alters expression of malignancy-related proteins in mesothelioma

Zeeshan Ahmad, Blake A. Jacobson, Mitchell W. McDonald, Nicolas Vattendahl Vidal, Gabriel Vattendahl Vidal, Sierra Chen, Maxwell Dillenburg, Aniekan M. Okon, Manish R. Patel, Carston R. Wagner, Robert A. Kratzke

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

6 Scopus citations

Abstract

Activated cap-dependent translation promotes cancer by stimulating translation of mRNAs encoding malignancy-promoting proteins. The nucleoside monophosphate Protide, 4Ei-10, undergoes intracellular uptake and conversion by Hint1 to form 7-Cl-Ph-Ethyl-GMP. 7-Cl-Ph-Ethyl-GMP is an analog of cap and inhibits protein translation by binding and sequestering eIF4E thus blocking eIF4E from binding to the mRNA cap. The effects of inhibiting translation initiation by disruption of the eIF4F complex with 4Ei-10 were examined in malignant mesothelioma (MM). In a cell-free assay system, formation of the eIF4F complex was disabled in response to exposure to 4Ei-10. Treatment of MM with 4Ei-10 resulted in decreased cell proliferation, increased sensitivity to pemetrexed and altered expression of malignancy-related proteins. In light of these findings, suppression of translation initiation by small molecule inhibitors like 4Ei-10 alone or in combination with pemetrexed represents an encouraging strategy meriting further evaluation in the treatment of MM.

Original language	English (US)
Pages (from-to)	425-432
Number of pages	8
Journal	Cancer chemotherapy and pharmacology
Volume	85
Issue number	2
DOIs	https://doi.org/10.1007/s00280-020-04029-9
State	Published - Feb 1 2020

Bibliographical note

Funding Information:
This work was supported in part by the Harvey Carlson Mesothelioma Research Fund. All authors have read the journal's authorship agreement and the policy on potential conflicts of interest.

Funding Information:
This work was funded in part by the Harvey Carlson Mesothelioma Research Fund of the University of Minnesota. Acknowledgements

Publisher Copyright:
© 2020, Springer-Verlag GmbH Germany, part of Springer Nature.

Keywords

4Ei-10
7-Cl-Ph-Ethyl-GMP
Cap-dependent translation
Mesothelioma
ProTide
eIF4E
eIF4G

PubMed: MeSH publication types

Journal Article
Research Support, Non-U.S. Gov't

UN SDGs

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

Publisher link

10.1007/s00280-020-04029-9

Find It

Find It at U of M Libraries

Cite this

Ahmad, Z., Jacobson, B. A., McDonald, M. W., Vattendahl Vidal, N., Vattendahl Vidal, G., Chen, S., Dillenburg, M., Okon, A. M., Patel, M. R., Wagner, C. R., & Kratzke, R. A. (2020). Repression of oncogenic cap-mediated translation by 4Ei-10 diminishes proliferation, enhances chemosensitivity and alters expression of malignancy-related proteins in mesothelioma. Cancer chemotherapy and pharmacology, 85(2), 425-432. https://doi.org/10.1007/s00280-020-04029-9

Repression of oncogenic cap-mediated translation by 4Ei-10 diminishes proliferation, enhances chemosensitivity and alters expression of malignancy-related proteins in mesothelioma. / Ahmad, Zeeshan; Jacobson, Blake A.; McDonald, Mitchell W. et al.
In: Cancer chemotherapy and pharmacology, Vol. 85, No. 2, 01.02.2020, p. 425-432.

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

Ahmad, Z, Jacobson, BA, McDonald, MW, Vattendahl Vidal, N, Vattendahl Vidal, G, Chen, S, Dillenburg, M, Okon, AM, Patel, MR , Wagner, CR & Kratzke, RA 2020, 'Repression of oncogenic cap-mediated translation by 4Ei-10 diminishes proliferation, enhances chemosensitivity and alters expression of malignancy-related proteins in mesothelioma', Cancer chemotherapy and pharmacology, vol. 85, no. 2, pp. 425-432. https://doi.org/10.1007/s00280-020-04029-9

@article{c15893bfe6cd485facbc81978736798b,

title = "Repression of oncogenic cap-mediated translation by 4Ei-10 diminishes proliferation, enhances chemosensitivity and alters expression of malignancy-related proteins in mesothelioma",

abstract = "Activated cap-dependent translation promotes cancer by stimulating translation of mRNAs encoding malignancy-promoting proteins. The nucleoside monophosphate Protide, 4Ei-10, undergoes intracellular uptake and conversion by Hint1 to form 7-Cl-Ph-Ethyl-GMP. 7-Cl-Ph-Ethyl-GMP is an analog of cap and inhibits protein translation by binding and sequestering eIF4E thus blocking eIF4E from binding to the mRNA cap. The effects of inhibiting translation initiation by disruption of the eIF4F complex with 4Ei-10 were examined in malignant mesothelioma (MM). In a cell-free assay system, formation of the eIF4F complex was disabled in response to exposure to 4Ei-10. Treatment of MM with 4Ei-10 resulted in decreased cell proliferation, increased sensitivity to pemetrexed and altered expression of malignancy-related proteins. In light of these findings, suppression of translation initiation by small molecule inhibitors like 4Ei-10 alone or in combination with pemetrexed represents an encouraging strategy meriting further evaluation in the treatment of MM.",

keywords = "4Ei-10, 7-Cl-Ph-Ethyl-GMP, Cap-dependent translation, Mesothelioma, ProTide, eIF4E, eIF4G",

author = "Zeeshan Ahmad and Jacobson, {Blake A.} and McDonald, {Mitchell W.} and {Vattendahl Vidal}, Nicolas and {Vattendahl Vidal}, Gabriel and Sierra Chen and Maxwell Dillenburg and Okon, {Aniekan M.} and Patel, {Manish R.} and Wagner, {Carston R.} and Kratzke, {Robert A.}",

note = "Funding Information: This work was supported in part by the Harvey Carlson Mesothelioma Research Fund. All authors have read the journal's authorship agreement and the policy on potential conflicts of interest. Funding Information: This work was funded in part by the Harvey Carlson Mesothelioma Research Fund of the University of Minnesota. Acknowledgements Publisher Copyright: {\textcopyright} 2020, Springer-Verlag GmbH Germany, part of Springer Nature.",

year = "2020",

month = feb,

day = "1",

doi = "10.1007/s00280-020-04029-9",

language = "English (US)",

volume = "85",

pages = "425--432",

journal = "Cancer chemotherapy and pharmacology",

issn = "0344-5704",

publisher = "Springer Verlag",

number = "2",

}

TY - JOUR

T1 - Repression of oncogenic cap-mediated translation by 4Ei-10 diminishes proliferation, enhances chemosensitivity and alters expression of malignancy-related proteins in mesothelioma

AU - Ahmad, Zeeshan

AU - Jacobson, Blake A.

AU - McDonald, Mitchell W.

AU - Vattendahl Vidal, Nicolas

AU - Vattendahl Vidal, Gabriel

AU - Chen, Sierra

AU - Dillenburg, Maxwell

AU - Okon, Aniekan M.

AU - Patel, Manish R.

AU - Wagner, Carston R.

AU - Kratzke, Robert A.

N1 - Funding Information: This work was supported in part by the Harvey Carlson Mesothelioma Research Fund. All authors have read the journal's authorship agreement and the policy on potential conflicts of interest. Funding Information: This work was funded in part by the Harvey Carlson Mesothelioma Research Fund of the University of Minnesota. Acknowledgements Publisher Copyright: © 2020, Springer-Verlag GmbH Germany, part of Springer Nature.

PY - 2020/2/1

Y1 - 2020/2/1

N2 - Activated cap-dependent translation promotes cancer by stimulating translation of mRNAs encoding malignancy-promoting proteins. The nucleoside monophosphate Protide, 4Ei-10, undergoes intracellular uptake and conversion by Hint1 to form 7-Cl-Ph-Ethyl-GMP. 7-Cl-Ph-Ethyl-GMP is an analog of cap and inhibits protein translation by binding and sequestering eIF4E thus blocking eIF4E from binding to the mRNA cap. The effects of inhibiting translation initiation by disruption of the eIF4F complex with 4Ei-10 were examined in malignant mesothelioma (MM). In a cell-free assay system, formation of the eIF4F complex was disabled in response to exposure to 4Ei-10. Treatment of MM with 4Ei-10 resulted in decreased cell proliferation, increased sensitivity to pemetrexed and altered expression of malignancy-related proteins. In light of these findings, suppression of translation initiation by small molecule inhibitors like 4Ei-10 alone or in combination with pemetrexed represents an encouraging strategy meriting further evaluation in the treatment of MM.

AB - Activated cap-dependent translation promotes cancer by stimulating translation of mRNAs encoding malignancy-promoting proteins. The nucleoside monophosphate Protide, 4Ei-10, undergoes intracellular uptake and conversion by Hint1 to form 7-Cl-Ph-Ethyl-GMP. 7-Cl-Ph-Ethyl-GMP is an analog of cap and inhibits protein translation by binding and sequestering eIF4E thus blocking eIF4E from binding to the mRNA cap. The effects of inhibiting translation initiation by disruption of the eIF4F complex with 4Ei-10 were examined in malignant mesothelioma (MM). In a cell-free assay system, formation of the eIF4F complex was disabled in response to exposure to 4Ei-10. Treatment of MM with 4Ei-10 resulted in decreased cell proliferation, increased sensitivity to pemetrexed and altered expression of malignancy-related proteins. In light of these findings, suppression of translation initiation by small molecule inhibitors like 4Ei-10 alone or in combination with pemetrexed represents an encouraging strategy meriting further evaluation in the treatment of MM.

KW - 4Ei-10

KW - 7-Cl-Ph-Ethyl-GMP

KW - Cap-dependent translation

KW - Mesothelioma

KW - ProTide

KW - eIF4E

KW - eIF4G

UR - http://www.scopus.com/inward/record.url?scp=85078087144&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85078087144&partnerID=8YFLogxK

U2 - 10.1007/s00280-020-04029-9

DO - 10.1007/s00280-020-04029-9

M3 - Article

C2 - 31974652

AN - SCOPUS:85078087144

SN - 0344-5704

VL - 85

SP - 425

EP - 432

JO - Cancer chemotherapy and pharmacology

JF - Cancer chemotherapy and pharmacology

IS - 2

ER -

Repression of oncogenic cap-mediated translation by 4Ei-10 diminishes proliferation, enhances chemosensitivity and alters expression of malignancy-related proteins in mesothelioma

Abstract

Bibliographical note

Keywords

PubMed: MeSH publication types

UN SDGs

Publisher link

Find It

Other files and links

Fingerprint

Cite this