Menu
×
Main Library
9 a.m. - 6 p.m.
Phone: (843) 805-6930
West Ashley Library
9 a.m. - 4 p.m.
Phone: (843) 766-6635
Folly Beach Library
Closed for renovations
Phone: (843) 588-2001
John L. Dart Library
9 a.m. - 6 p.m.
Phone: (843) 722-7550
St. Paul's/Hollywood Library
9 a.m. - 5 p.m.
Phone: (843) 889-3300
Mt. Pleasant Library
9 a.m. – 6 p.m.
Phone: (843) 849-6161
Dorchester Road Library
9 a.m. - 6 p.m.
Phone: (843) 552-6466
Edgar Allan Poe/Sullivan's Island Library
9 a.m. - 6 p.m.
Phone: (843) 883-3914
John's Island Library
9 a.m. - 6 p.m.
Phone: (843) 559-1945
McClellanville Library
Closed for renovations
Phone: (843) 887-3699
Edisto Library
9 a.m. - 3 p.m.
Phone: (843) 869-2355
Wando Mount Pleasant Library
9 a.m. - 6 p.m.
Phone: (843) 805-6888
Otranto Road Library
9 a.m. - 6 p.m.
Phone: (843) 572-4094
Hurd/St. Andrews Library
9 a.m. - 6 p.m.
Phone: (843) 766-2546
Baxter-Patrick James Island
9 a.m. - 6 p.m.
Phone: (843) 795-6679
Bees Ferry West Ashley Library
9 a.m. - 6 p.m.
Phone: (843) 805-6892
Village Library
9 a.m. - 6 p.m.
Phone: (843) 884-9741
Keith Summey North Charleston Library
9 a.m. – 6 p.m.
Phone: (843) 744-2489
Mobile Library
9 a.m. - 5 p.m.
Phone: (843) 805-6909
Today's Hours
Main Library
9 a.m. - 6 p.m.
Phone: (843) 805-6930
West Ashley Library
9 a.m. - 4 p.m.
Phone: (843) 766-6635
Folly Beach Library
Closed for renovations
Phone: (843) 588-2001
John L. Dart Library
9 a.m. - 6 p.m.
Phone: (843) 722-7550
St. Paul's/Hollywood Library
9 a.m. - 5 p.m.
Phone: (843) 889-3300
Mt. Pleasant Library
9 a.m. – 6 p.m.
Phone: (843) 849-6161
Dorchester Road Library
9 a.m. - 6 p.m.
Phone: (843) 552-6466
Edgar Allan Poe/Sullivan's Island Library
9 a.m. - 6 p.m.
Phone: (843) 883-3914
John's Island Library
9 a.m. - 6 p.m.
Phone: (843) 559-1945
McClellanville Library
Closed for renovations
Phone: (843) 887-3699
Edisto Library
9 a.m. - 3 p.m.
Phone: (843) 869-2355
Wando Mount Pleasant Library
9 a.m. - 6 p.m.
Phone: (843) 805-6888
Otranto Road Library
9 a.m. - 6 p.m.
Phone: (843) 572-4094
Hurd/St. Andrews Library
9 a.m. - 6 p.m.
Phone: (843) 766-2546
Baxter-Patrick James Island
9 a.m. - 6 p.m.
Phone: (843) 795-6679
Bees Ferry West Ashley Library
9 a.m. - 6 p.m.
Phone: (843) 805-6892
Village Library
9 a.m. - 6 p.m.
Phone: (843) 884-9741
Keith Summey North Charleston Library
9 a.m. – 6 p.m.
Phone: (843) 744-2489
Mobile Library
9 a.m. - 5 p.m.
Phone: (843) 805-6909
Patron Login
menu
Item request has been placed!
×
Item request cannot be made.
×
Processing Request
Apoptosis induced by depsipeptide FK228 coincides with inhibition of survival signaling in lung cancer cells.
Item request has been placed!
×
Item request cannot be made.
×
Processing Request
- Author(s): Yu X; Wang S; Chen A; Hou C; Zhao M; Hong JA; Nguyen DM; Schrump DS; Yu, Xiao-Dan; Wang, Sheng-Yu; Chen, G Aaron; Hou, Chun-Mei; Zhao, Ming; Hong, Julie A; Nguyen, Dao M; Schrump, David S
- Source:
Cancer Journal; Mar/Apr2007, Vol. 13 Issue 2, p105-113, 9p - Source:
- Additional Information
- Abstract:
Background: Whereas histone deacetylase inhibitors are known to modulate chromatin structure, the precise mechanisms by which these novel agents induce apoptosis in cancer cells remain unknown. Previously we reported that depsipeptide FK228 depletes epidermal growth factor receptor (EGFR), erbB2, and Raf-1 kinases in non-small cell lung cancer cells. In the present study we sought to further define the mechanisms by which FK228 modulates oncoprotein signaling and to ascertain whether altered signal transduction contributes to FK228-mediated apoptosis in lung cancer cells.Methods: Cultured non-small cell lung cancer cells were treated with FK228 alone or FK228 with a variety of kinase inhibitors. Proliferation and apoptosis mediated by drug exposure were assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium, and Apo-BrdU techniques. Western blot and kinase assays were used to evaluate EGFR-related signal transduction pathways. Lung cancer cells were transduced with adenoviral vectors expressing activated AKT or mitogen-activated protein kinase kinase (MEK) 1 or beta-galactosidase to determine whether constitutive activation of mitogen-activated protein kinase signaling could abrogate FK228-mediated apoptosis.Results: FK228 treatment induced time-dependent apoptosis in lung cancer cells expressing wild-type or mutant EGFR. FK228 inhibited a variety of EGFR-related pathways including Src, RAF-MEK-extracellular signal-regulated kinase (ERK) 1/2 and phosphatidyl inositol-3 kinase (PI3K)/AKT, resulting in down-regulation of Bcl-2 and Bcl-xL and up-regulation of Bax. The kinase inhibitors AG1478, AG825, PD98059, and LY294002 markedly enhanced FK228-induced apoptosis in lung cancer cells. Coincident with inhibition of ERK1/2 and PI3K/AKT survival pathways, FK228 enhanced p38 and stress-activated protein kinase/c-Jun NH2-terminal kinase stress signaling. Constitutive expression of MEK1 but not AKT markedly reduced FK228-mediated apoptosis in lung cancer cells.Conclusions: FK228 inhibits EGFR expression and modulates a variety of downstream mediators regulating proliferation and stress responses in lung cancer cells. These data highlight the significance of MEK signaling with respect to FK228-mediated apoptosis and support evaluation of histone deacetylase inhibitors in conjunction with agents specifically targeting mitogen-activated protein kinases in patients with lung cancer. [ABSTRACT FROM AUTHOR] - Abstract: Copyright of Cancer Journal is the property of Lippincott Williams & Wilkins and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
- Abstract:
Contact CCPL
Copyright 2022 Charleston County Public Library Powered By EBSCO Stacks 3.3.0 [350.3] | Staff Login
No Comments.