Anti-tumor effects by a synthetic chalcone compound is mediated by c-Myc-mediated reactive oxygen species production.
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.
Kim
Tae-Hee
TH
Division of Radiation Effects, Korea Institute of Radiological and Medical Sciences, 215-4 Gongneung-Dong, Nowon-Ku, Seoul 139-706, Republic of Korea.
Seo
Woo Duck
WD
Ryu
Hyung Won
HW
Seo
Haeng Ran
HR
Jin
Yeung Bae
YB
Lee
Minyoung
M
Ji
Young-Hoon
YH
Park
Ki Hun
KH
Lee
Yun-Sil
YS
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D015153:Blotting, Western; D045744:Cell Line, Tumor; D047188:Chalcones / Q000494:pharmacology*; D005434:Flow Cytometry; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism*
D000970:Antineoplastic Agents; D047188:Chalcones; D016271:Proto-Oncogene Proteins c-myc; D017382:Reactive Oxygen Species