Induction of oncogene addiction shift to NF-{kappa}B by camptothecin in solid tumor cells

• Published in: Biochemical and biophysical research communications Vol. 390; no. 1
• Main Authors: Togano, Tomiteru, Sasaki, Masataka, Watanabe, Mariko, Nakashima, Makoto, Tsuruo, Takashi, Umezawa, Kazuo, Higashihara, Masaaki, Watanabe, Toshiki, Horie, Ryouichi
• Format: Journal Article
• Language: English
• Published: United States 04.12.2009
• Subjects: 60 APPLIED LIFE SCIENCES; CHEMOTHERAPY; LARGE INTESTINE; LUNGS; NEOPLASMS; ONCOGENES; TUMOR CELLS
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/J.BBRC.2009.09.066

The biological basis of the resistance of solid tumor cells to chemotherapy is not well understood. While addressing this problem, we found that gastric cancer cell line St-4/CPT, lung cancer cell line A549/CPT, and colon cancer cell line HT-29/CPT, all of which are resistant to camptothecin (CPT), showed strong and constitutive nuclear factor (NF)-{kappa}B activity driven by I{kappa}B kinase compared with their parental cell lines St-4, A549, and HT-29. A new NF-{kappa}B inhibitor, dehydroxymethylepoxyquinomicin (DHMEQ), reduced viability and induced apoptosis in St-4/CPT, A549/CPT, and HT-29/CPT cell lines, while their parental cell lines were resistant to DHMEQ. The results in this study present an example of the shift in signals that support the survival of solid tumor cells to NF-{kappa}B during the acquisition of resistance to CPT. The results also indicate that solid tumor cells that become resistant to chemotherapy may be more easily treated by NF-{kappa}B inhibitors.