A histone deacetylase inhibitor YCW1 with antitumor and antimetastasis properties enhances cisplatin activity against non-small cell lung cancer in preclinical studies
Journal
Cancer Letters
Journal Volume
346
Journal Issue
1
Pages
84-93
Date Issued
2014-04
Author(s)
Abstract
Many histone deacetylase (HDAC) inhibitors show limited therapeutic effects for solid tumors. Here, we develop a novel HDAC inhibitor YCW1 and verify the combination effect of YCW1 and cisplatin in lung cancer pre-clinical models. YCW1 exerted cancer-specific cytotoxicity via mitochondria-mediated apoptosis. YCW1 and cisplatin showed synergistic anti-tumor effects through impairment of DNA damage repair. YCW1 inhibited tumor growth in lung orthotopic and subcutaneously implanted xenograft models. YCW1 significantly suppressed lung metastases via inhibition of focal adhesion complex. Our findings suggested that YCW1 is a potential HDAC inhibitor for lung cancer treatment as single and in combination regimens with cisplatin. ? 2013 Elsevier Ireland Ltd.
Subjects
Apoptosis; Cisplatin; Histone deacetylase inhibitor; Metastasis; Non-small cell lung cancer
SDGs
Other Subjects
cisplatin; dimethyl sulfoxide; histone deacetylase inhibitor; octanedioic acid[3 [2(5 methoxy 1h indol 1 yl)ethoxy]phenyl]amide n hydroxymide; placebo; unclassified drug; vorinostat; animal cell; animal experiment; animal model; animal tissue; antineoplastic activity; article; BRCA2 gene; cancer combination chemotherapy; controlled study; DNA repair; down regulation; drug blood level; drug cytotoxicity; drug mechanism; drug potentiation; drug structure; drug targeting; female; focal adhesion; gene; gene expression regulation; human; human cell; IC 50; lung metastasis; lung non small cell cancer; male; maximum plasma concentration; metastasis inhibition; monotherapy; mouse; nonhuman; priority journal; RAD51 gene; structure activity relation; tumor xenograft; Apoptosis; Cisplatin; Histone deacetylase inhibitor; Metastasis; Non-small cell lung cancer; Animals; Antineoplastic Combined Chemotherapy Protocols; Azides; Carcinoma, Non-Small-Cell Lung; Cisplatin; Drug Synergism; Histone Deacetylase Inhibitors; Humans; Hydroxamic Acids; Lung Neoplasms; Male; Mice, Inbred BALB C; Reverse Transcriptase Polymerase Chain Reaction; Xenograft Model Antitumor Assays
Publisher
Elsevier Ireland Ltd.
Type
journal article