Journal
ANTICANCER RESEARCH
Volume 36, Issue 11, Pages 6083-6092Publisher
INT INST ANTICANCER RESEARCH
DOI: 10.21873/anticanres.11198
Keywords
Epigenetic; global histone modification; chemotherapy; clonogenic survival
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Funding
- Ministry of Education, Culture, Sports, Science and Technology of Japan
- Grants-in-Aid for Scientific Research [16K07160] Funding Source: KAKEN
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Background: GSKJ4, an H3K27 demethylase inhibitor, reportedly exhibits antitumor activity against specific cancers harboring genetic alterations in genes encoding chromatin modulators. However, its potential as an anticancer agent against human cancers not associated with such genetic alterations, including non-small cell lung cancer (NSCLC), remains unknown. Materials and Methods: The effect of GSKJ4 on the growth of three NSCLC cell lines and normal lung fibroblasts was investigated using the WST-8, dye exclusion, and colony formation assays. Results: GSKJ4, alone and in combination with an anti-diabetic drug metformin, induced cell death and inhibited the growth of NSCLC cell lines efficiently at concentrations non-toxic to normal cells, irrespective of their genetic backgrounds (mutations in the KRAS, TP53 and EGFR genes) and also of their resistance to cisplatin and paclitaxel. Conclusion: GSKJ4, being a promising anticancer agent for NSCLC, may be effective against a wider spectrum of cancers than previously thought.
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