Anti-tumor effect in human lung cancer by a combination treatment of novel histone deacetylase inhibitors: SL142 or SL325 and Retinoic acids

Shaoteng Han, Takuya Fukazawa, Tomoki Yamatsuji, Junji Matsuoka, Hiroyuki Miyachi, Yutaka Maeda, Mary Durbin, Yoshio Naomoto

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Histone deacetylase (HDAC) inhibitors arrest cancer cell growth and cause apoptosis with low toxicity thereby constituting a promising treatment for cancer. In this study, we investigated the anti-tumor activity in lung cancer cells of the novel cyclic amide-bearing hydroxamic acid based HDAC inhibitors SL142 and SL325. In A549 and H441 lung cancer cells both SL142 and SL325 induced more cell growth inhibition and cell death than the hydroxamic acid-based HDAC inhibitor suberoylanilide hydroxamic acid (SAHA). Moreover, the combination treatment using retinoid drugs ATRA or 9-cis RA along with SL142 or SL325 significantly induced more apoptosis and suppressed colony formation than the single use of either. The expression of the retinoic acid receptors RARa, RARb, RXRa and RXRb were unchanged with the treatment. However a luciferase reporter construct (pGL4. RARE 7x) containing seven tandem repeats of the retinoic acid responsible element (RARE) generated significant transcriptional activity after the combination treatment of retinoic acids and SL142 or SL325 in H441 lung cancer cells. Moreover, apoptosis-promoting Bax expression and caspase-3 activity was increased after the combination treatment. These results suggest that the combination treatment of SL142 or SL325 with retinoic acids exerts significant anti-tumor activity and is a promising therapeutic candidate to treat human lung cancer.

Original languageEnglish
Article numbere13834
JournalPLoS One
Volume5
Issue number11
DOIs
Publication statusPublished - 2010

Fingerprint

histone deacetylase
Histone Deacetylase Inhibitors
retinoic acid
lung neoplasms
Tretinoin
Tumors
Lung Neoplasms
hydroxamic acids
Hydroxamic Acids
neoplasms
Cells
Cell growth
Apoptosis
apoptosis
Neoplasms
Bearings (structural)
cell growth
Retinoic Acid Receptors
Tandem Repeat Sequences
Retinoids

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Anti-tumor effect in human lung cancer by a combination treatment of novel histone deacetylase inhibitors : SL142 or SL325 and Retinoic acids. / Han, Shaoteng; Fukazawa, Takuya; Yamatsuji, Tomoki; Matsuoka, Junji; Miyachi, Hiroyuki; Maeda, Yutaka; Durbin, Mary; Naomoto, Yoshio.

In: PLoS One, Vol. 5, No. 11, e13834, 2010.

Research output: Contribution to journalArticle

Han, Shaoteng ; Fukazawa, Takuya ; Yamatsuji, Tomoki ; Matsuoka, Junji ; Miyachi, Hiroyuki ; Maeda, Yutaka ; Durbin, Mary ; Naomoto, Yoshio. / Anti-tumor effect in human lung cancer by a combination treatment of novel histone deacetylase inhibitors : SL142 or SL325 and Retinoic acids. In: PLoS One. 2010 ; Vol. 5, No. 11.
@article{6ad523df2ad04a61a4373da8f27a8e3e,
title = "Anti-tumor effect in human lung cancer by a combination treatment of novel histone deacetylase inhibitors: SL142 or SL325 and Retinoic acids",
abstract = "Histone deacetylase (HDAC) inhibitors arrest cancer cell growth and cause apoptosis with low toxicity thereby constituting a promising treatment for cancer. In this study, we investigated the anti-tumor activity in lung cancer cells of the novel cyclic amide-bearing hydroxamic acid based HDAC inhibitors SL142 and SL325. In A549 and H441 lung cancer cells both SL142 and SL325 induced more cell growth inhibition and cell death than the hydroxamic acid-based HDAC inhibitor suberoylanilide hydroxamic acid (SAHA). Moreover, the combination treatment using retinoid drugs ATRA or 9-cis RA along with SL142 or SL325 significantly induced more apoptosis and suppressed colony formation than the single use of either. The expression of the retinoic acid receptors RARa, RARb, RXRa and RXRb were unchanged with the treatment. However a luciferase reporter construct (pGL4. RARE 7x) containing seven tandem repeats of the retinoic acid responsible element (RARE) generated significant transcriptional activity after the combination treatment of retinoic acids and SL142 or SL325 in H441 lung cancer cells. Moreover, apoptosis-promoting Bax expression and caspase-3 activity was increased after the combination treatment. These results suggest that the combination treatment of SL142 or SL325 with retinoic acids exerts significant anti-tumor activity and is a promising therapeutic candidate to treat human lung cancer.",
author = "Shaoteng Han and Takuya Fukazawa and Tomoki Yamatsuji and Junji Matsuoka and Hiroyuki Miyachi and Yutaka Maeda and Mary Durbin and Yoshio Naomoto",
year = "2010",
doi = "10.1371/journal.pone.0013834",
language = "English",
volume = "5",
journal = "PLoS One",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "11",

}

TY - JOUR

T1 - Anti-tumor effect in human lung cancer by a combination treatment of novel histone deacetylase inhibitors

T2 - SL142 or SL325 and Retinoic acids

AU - Han, Shaoteng

AU - Fukazawa, Takuya

AU - Yamatsuji, Tomoki

AU - Matsuoka, Junji

AU - Miyachi, Hiroyuki

AU - Maeda, Yutaka

AU - Durbin, Mary

AU - Naomoto, Yoshio

PY - 2010

Y1 - 2010

N2 - Histone deacetylase (HDAC) inhibitors arrest cancer cell growth and cause apoptosis with low toxicity thereby constituting a promising treatment for cancer. In this study, we investigated the anti-tumor activity in lung cancer cells of the novel cyclic amide-bearing hydroxamic acid based HDAC inhibitors SL142 and SL325. In A549 and H441 lung cancer cells both SL142 and SL325 induced more cell growth inhibition and cell death than the hydroxamic acid-based HDAC inhibitor suberoylanilide hydroxamic acid (SAHA). Moreover, the combination treatment using retinoid drugs ATRA or 9-cis RA along with SL142 or SL325 significantly induced more apoptosis and suppressed colony formation than the single use of either. The expression of the retinoic acid receptors RARa, RARb, RXRa and RXRb were unchanged with the treatment. However a luciferase reporter construct (pGL4. RARE 7x) containing seven tandem repeats of the retinoic acid responsible element (RARE) generated significant transcriptional activity after the combination treatment of retinoic acids and SL142 or SL325 in H441 lung cancer cells. Moreover, apoptosis-promoting Bax expression and caspase-3 activity was increased after the combination treatment. These results suggest that the combination treatment of SL142 or SL325 with retinoic acids exerts significant anti-tumor activity and is a promising therapeutic candidate to treat human lung cancer.

AB - Histone deacetylase (HDAC) inhibitors arrest cancer cell growth and cause apoptosis with low toxicity thereby constituting a promising treatment for cancer. In this study, we investigated the anti-tumor activity in lung cancer cells of the novel cyclic amide-bearing hydroxamic acid based HDAC inhibitors SL142 and SL325. In A549 and H441 lung cancer cells both SL142 and SL325 induced more cell growth inhibition and cell death than the hydroxamic acid-based HDAC inhibitor suberoylanilide hydroxamic acid (SAHA). Moreover, the combination treatment using retinoid drugs ATRA or 9-cis RA along with SL142 or SL325 significantly induced more apoptosis and suppressed colony formation than the single use of either. The expression of the retinoic acid receptors RARa, RARb, RXRa and RXRb were unchanged with the treatment. However a luciferase reporter construct (pGL4. RARE 7x) containing seven tandem repeats of the retinoic acid responsible element (RARE) generated significant transcriptional activity after the combination treatment of retinoic acids and SL142 or SL325 in H441 lung cancer cells. Moreover, apoptosis-promoting Bax expression and caspase-3 activity was increased after the combination treatment. These results suggest that the combination treatment of SL142 or SL325 with retinoic acids exerts significant anti-tumor activity and is a promising therapeutic candidate to treat human lung cancer.

UR - http://www.scopus.com/inward/record.url?scp=78149491383&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=78149491383&partnerID=8YFLogxK

U2 - 10.1371/journal.pone.0013834

DO - 10.1371/journal.pone.0013834

M3 - Article

C2 - 21079797

AN - SCOPUS:78149491383

VL - 5

JO - PLoS One

JF - PLoS One

SN - 1932-6203

IS - 11

M1 - e13834

ER -