Hikaru Watarai1,2, Masashi Okada3, Kenta Kuramoto1, Hiroyuki Takeda1,4, Hirotsugu Sakaki1,5, Shuhei Suzuki1,4, Shizuka Seino1,6, Hiroyuki Oizumi2, Mitsuaki Sadahiro2, Chifumi Kitanaka3,6. 1. Department of Molecular Cancer Science, Yamagata University School of Medicine, Yamagata, Japan. 2. Second Department of Surgery, Yamagata University School of Medicine, Yamagata, Japan. 3. Department of Molecular Cancer Science, Yamagata University School of Medicine, Yamagata, Japan ckitanak@med.id.yamagata-u.ac.jp m-okada@med.id.yamagata-u.ac.jp. 4. Department of Obstetrics and Gynecology, Yamagata University School of Medicine, Yamagata, Japan. 5. Department of Clinical Oncology, Yamagata University School of Medicine, Yamagata, Japan. 6. Research Institute for Promotion of Medical Sciences, Yamagata University Faculty of Medicine, Yamagata, Japan.
Abstract
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. Copyright
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 humancancers 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. Copyright