Antitumor activity of BJ-1207, a 6-amino-2,4,5-trimethylpyridin-3-ol derivative, in human lung cancer
- Authors
- Gautam, Jaya; Banskota, Suhrid; Chaudhary, Prakash; Dahal, Sadan; Kim, Dong-Guk; Kang, Han-eol; Lee, Iyn-Hyang; Nam, Tae-Gyu; Jeong, Byeong-Seon; Kim, Jung-Ae
- Issue Date
- Oct-2018
- Publisher
- ELSEVIER IRELAND LTD
- Keywords
- Aminopyridin-3-ols; Non-small cell lung cancer; NADPH oxidase; Stem cell factor; Transforming growth factor-alpha
- Citation
- CHEMICO-BIOLOGICAL INTERACTIONS, v.294, pp.1 - 8
- Indexed
- SCIE
SCOPUS
- Journal Title
- CHEMICO-BIOLOGICAL INTERACTIONS
- Volume
- 294
- Start Page
- 1
- End Page
- 8
- URI
- https://scholarworks.bwise.kr/erica/handle/2021.sw.erica/5251
- DOI
- 10.1016/j.cbi.2018.08.007
- ISSN
- 0009-2797
- Abstract
- Enhanced expression of NADPH oxidase (NOX) and the subsequent production of reactive oxygen species (ROS) are associated with lung cancer. In the present study, fifty 6-amino-2,4,5-trimethylpyridin-3-ol derivatives were screened for anticancer activity by targeting NOX2-derived ROS. The compounds suppressed ROS production and decreased cancer cell viability (R-2= 0.79). Among the derivatives, the compound coded BJ-1207, which contained a 4-(hydroxydiphenylmethyl) piperidine moiety, exhibited the most effective anticancer activity against A549 lung cancer cell line and eight other cancer cell lines, including H1299, MCF-7, MDA-MB-231, HT29, SW620, Mia PaCa-2, PANC-1, and U937. BJ-1207 also showed significantly lower inhibitory effects on kinase insert domain receptor (KDR) and c-KIT tyrosine kinase but higher inhibitory activity on NOX than those of sunitinib, a multi-receptor tyrosine kinase (RTK) inhibitor. In addition, BJ-1207-induced inhibition of RTK-downstream signaling pathways, such as ROS production, and expression of target genes, such as stem cell factor and transforming growth factor-alpha, were similar to those induced by sunitinib. In the xenograft chick tumor model, BJ-1207 inhibited lung tumor growth to a similar or much greater extent than that of sunitinib or cisplatin, respectively. Overall, the present study showed that BJ-1207, a vitamin B-6-derived 2,4,5-trimethylpyridin-3-ol compound with azacyclonol moiety at C (6)-position of the pyridine ring, inhibited NOX activity and that it is a promising lead compound for developing anticancer drugs against lung cancer.
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