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Anti-tumor effects by a synthetic chalcone compound is mediated by c-Myc-mediated reactive oxygen species production

2010; Elsevier BV; Volume: 188; Issue: 1 Linguagem: Inglês

10.1016/j.cbi.2010.06.016

1872-7786

Tae Hee Kim, Woo Duck Seo, Hyung Won Ryu, Haeng Ran Seo, Yeung Bae Jin, Minyoung Lee, Younghoon Ji, Ki Hun Park, Yun‐Sil Lee,

Cancer therapeutics and mechanisms

Overexpression of c-Myc represents the most frequently deregulated genetic event in cancer, and therefore c-Myc may represent a good molecular target for cancer therapy. The human lung carcinoma cell line, NCI-H1299, shows resistance to conventional cancer treatments, such as ionizing radiation (IR) and cisplatin, while the lung carcinoma cell line, NCI-H460, is sensitive to treatment with these agents. However, when treated with a chalcone compound [toluenesulfonylamido-chalcone, 4'-(p-toluene sulfonyl amino)-3,4-dihydroxy chalcone (TSHDC)], cell death was dramatically induced in NCI-H1299 cells as compared to NCI-H460 cells. TSHDC-mediated cytotoxicity was not dependent on the status of p53 and p21. However, TSHDC exerted increased c-Myc-dependent reactive oxygen species (ROS) production in NCI-H1299 cells in which c-Myc is overexpressed, while increased ROS production did not occur in A549 or NCI-H460 cells with a low c-Myc level. Several colon and brain cancer cells also showed a correlation between c-Myc expression and TSHDC-mediated increased cell death. Tumor regression by TSHDC was more dramatic in NCI-H1299 cells than NCI-H460 cells, when these cells were grafted to nude mice. However, in the case of IR and cisplatin, NCI-H460 cells were more sensitive than NCI-H1299 cells. From these results, c-Myc-mediated ROS production may be a good target for screening of novel cancer drugs and TSHDC might be a good candidate as a cancer drug, specifically in cancer cells that overexpress c-Myc.