24 0

Dual Inhibition of NOX2 and Receptor Tyrosine Kinase by BJ-1301 Enhances Anticancer Therapy Efficacy via Suppression of Autocrine-Stimulatory Factors in Lung Cancer

Title
Dual Inhibition of NOX2 and Receptor Tyrosine Kinase by BJ-1301 Enhances Anticancer Therapy Efficacy via Suppression of Autocrine-Stimulatory Factors in Lung Cancer
Author
남태규
Keywords
ENDOTHELIAL GROWTH-FACTOR; NADPH OXIDASES; ALPHA-TOCOPHEROL; HYDROGEN-PEROXIDE; EPITHELIAL-CELLS; VITAMIN-E; ANGIOGENESIS; KIT; METAANALYSIS; TOCOTRIENOL
Issue Date
2017-10
Publisher
AMER ASSOC CANCER RESEARCH
Citation
MOLECULAR CANCER THERAPEUTICS, v. 16, No. 10, Page. 2144-2156
Abstract
NADPH oxidase-derived reactive oxygen species (ROS) potentiate receptor tyrosine kinase (RTK) signaling, resulting in enhanced angiogenesis and tumor growth. In this study, we report that BJ-1301, a hybrid of pyridinol and alpha-tocopherol, exerts anticancer effects by dual inhibition of NADPH oxidase and RTK activities in endothelial and lung cancer cells. BJ-1301 suppresses ROS production by blocking translocation of NADPH oxidase cytosolic subunits to the cell membrane, thereby inhibiting activation. The potency of RTK inhibition by BJ-1301 was lower than that of sunitinib (a multi-RTK inhibitor), but the inhibition of downstream signaling pathways (e.g., ROS generation) and subsequent biological changes (e.g., NOX2 induction) by BJ-1301 was superior. Consistently, BJ-1301 inhibited cisplatin-resistant lung cancer cell proliferation more than sunitinib did. In xenograft chick or mouse tumor models, BJ-1301 inhibited lung tumor growth, to an extent greater than that of sunitinib or cisplatin. Treatments with BJ-1301 induced regression of tumor growth, potentially due to downregulation of autocrine-stimulatory ligands for RTKs, such as TGFa and stem cell factor, in tumor tissues. Taken together, the current study demonstrates that BJ-1301 is a promising anticancer drug for the treatment of lung cancer.
URI
http://mct.aacrjournals.org/content/early/2017/05/23/1535-7163.MCT-16-0915http://repository.hanyang.ac.kr/handle/20.500.11754/103699
ISSN
1538-8514; 1535-7163
DOI
10.1158/1535-7163.MCT-16-0915
Appears in Collections:
COLLEGE OF PHARMACY[E](약학대학) > PHARMACY(약학과) > Articles
Files in This Item:
There are no files associated with this item.
Export
RIS (EndNote)
XLS (Excel)
XML


qrcode

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

BROWSE