Antibiotic drug rifabutin is effective against lung cancer cells by targeting the eIF4E-β-catenin axis
Abstract
The essential roles of overexpression of eukaryotic translation initiation factor 4E (eIF4E) and aberrant activation of β-catenin in lung cancer development have been recently identified. However, whether there is a direct connection between eIF4E overexpression and β-catenin activation in lung cancer cells is unknown. In this study, we show that antibiotic drug rifabutin targets human lung cancer cells via inhibition of eIF4E-β-catenin axis. Rifabutin is effectively against lung cancer cells in in vitro cultured cells and in vivo xenograft mouse model through inhibiting proliferation and inducing apoptosis. Mechanistically, eIF4E regulates β-catenin activity in lung cancer cells as shown by the increased β-catenin phosphorylation and activity in cells overexpressing eIF4E, and furthermore that the regulation is dependent on phosphorylation at S209. Rifabutin suppresses eIF4E phosphorylation, leads to decreased β-catenin phosphorylation and its subsequent transcriptional activities. Depletion of eIF4E abolishes the inhibitory effects of rifabutin on β-catenin activities and overexpression of β-catenin reverses the inhibitory effects of rifabutin on cell growth and survival, further confirming that rifabutin acts on lung cancer cells via targeting eIF4E- β-catenin axis. Our findings identify the eIF4E- β-catenin axis as a critical regulator of lung cancer cell growth and survival, and suggest that its pharmacological inhibition may be therapeuticallymore »
- Authors:
-
- Department of Respiratory Medicine, Hainan General Hospital, Hainan Province (China)
- Equipment Division, Hainan General Hospital, Hainan Province (China)
- Department of Ophthalmology, Hainan Eye Hospital, ZhongShan Ophthalmic Centre, Sun Yat-Sen University, Hainan Province (China)
- Publication Date:
- OSTI Identifier:
- 22596314
- Resource Type:
- Journal Article
- Journal Name:
- Biochemical and Biophysical Research Communications
- Additional Journal Information:
- Journal Volume: 472; Journal Issue: 2; Other Information: Copyright (c) 2016 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0006-291X
- Country of Publication:
- United States
- Language:
- English
- Subject:
- 60 APPLIED LIFE SCIENCES; ANTIBIOTICS; APOPTOSIS; CELL CULTURES; IN VITRO; IN VIVO; INHIBITION; LUNGS; MICE; NEOPLASMS; PHOSPHORYLATION; PLANT GROWTH
Citation Formats
Li, Ji, Huang, Yijiang, Gao, Yunsuo, Wu, Haihong, Dong, Wen, and Liu, Lina. Antibiotic drug rifabutin is effective against lung cancer cells by targeting the eIF4E-β-catenin axis. United States: N. p., 2016.
Web. doi:10.1016/J.BBRC.2016.02.120.
Li, Ji, Huang, Yijiang, Gao, Yunsuo, Wu, Haihong, Dong, Wen, & Liu, Lina. Antibiotic drug rifabutin is effective against lung cancer cells by targeting the eIF4E-β-catenin axis. United States. https://doi.org/10.1016/J.BBRC.2016.02.120
Li, Ji, Huang, Yijiang, Gao, Yunsuo, Wu, Haihong, Dong, Wen, and Liu, Lina. 2016.
"Antibiotic drug rifabutin is effective against lung cancer cells by targeting the eIF4E-β-catenin axis". United States. https://doi.org/10.1016/J.BBRC.2016.02.120.
@article{osti_22596314,
title = {Antibiotic drug rifabutin is effective against lung cancer cells by targeting the eIF4E-β-catenin axis},
author = {Li, Ji and Huang, Yijiang and Gao, Yunsuo and Wu, Haihong and Dong, Wen and Liu, Lina},
abstractNote = {The essential roles of overexpression of eukaryotic translation initiation factor 4E (eIF4E) and aberrant activation of β-catenin in lung cancer development have been recently identified. However, whether there is a direct connection between eIF4E overexpression and β-catenin activation in lung cancer cells is unknown. In this study, we show that antibiotic drug rifabutin targets human lung cancer cells via inhibition of eIF4E-β-catenin axis. Rifabutin is effectively against lung cancer cells in in vitro cultured cells and in vivo xenograft mouse model through inhibiting proliferation and inducing apoptosis. Mechanistically, eIF4E regulates β-catenin activity in lung cancer cells as shown by the increased β-catenin phosphorylation and activity in cells overexpressing eIF4E, and furthermore that the regulation is dependent on phosphorylation at S209. Rifabutin suppresses eIF4E phosphorylation, leads to decreased β-catenin phosphorylation and its subsequent transcriptional activities. Depletion of eIF4E abolishes the inhibitory effects of rifabutin on β-catenin activities and overexpression of β-catenin reverses the inhibitory effects of rifabutin on cell growth and survival, further confirming that rifabutin acts on lung cancer cells via targeting eIF4E- β-catenin axis. Our findings identify the eIF4E- β-catenin axis as a critical regulator of lung cancer cell growth and survival, and suggest that its pharmacological inhibition may be therapeutically useful in lung cancer. - Highlights: • Rifabutin targets EGFR-mutated lung cancer cells in vitro and in vivo. • eIF4E phosphorylation regulates β-catenin activity in lung cancer cells. • Rifabutin acts on lung cancer cells via eIF4E- β-catenin axis. • Rifabutin can be repurposed for lung cancer treatment.},
doi = {10.1016/J.BBRC.2016.02.120},
url = {https://www.osti.gov/biblio/22596314},
journal = {Biochemical and Biophysical Research Communications},
issn = {0006-291X},
number = 2,
volume = 472,
place = {United States},
year = {Fri Apr 01 00:00:00 EDT 2016},
month = {Fri Apr 01 00:00:00 EDT 2016}
}