Selective cytotoxicity of ascochlorin in ER-negative human breast cancer cell lines.
While agents targeting estrogen receptors are most effective in adjuvant therapy for human breast cancers expressing estrogen receptors after surgery, breast cancers lacking estrogen receptor are clinically serious, because they are highly malignant and exhibit resistance to the usual anti-cancer drugs, including estrogen receptor-antagonists and DNA breaking agents. Here, we found that MX-1, a human breast cancer cell line lacking estrogen receptors, exhibited higher AP-1 activity and expressed higher levels of c-Jun, c-Fos, and Fra-1 when compared with conventional estrogen receptor-positive human breast cancer cell lines. The prenylphenol antibiotic ascochlorin suppressed the AP-1 activity of MX-1 cells, and selectively killed MX-1 cells, partly due to induction of apoptosis. Our results suggest that AP-1 is an effective clinical target molecule for the treatment of estrogen receptor-negative human breast cancer.
Sakaguchi
Koichi
K
Department of Endocrine, Breast Surgery, Kyoto Prefectural University of Medicine, Kawaramachi, Hirokoji, Kamikyo-ku, Kyoto 602-0841, Japan.
Nakajima
Hiroo
H
Mizuta
Naruhiko
N
Furukawa
Chiharu
C
Ozawa
Satoshi
S
Ando
Kunio
K
Chang
Young-Chae
YC
Yamagishi
Hisakazu
H
Magae
Junji
J
D000475:Alkenes / Q000494:pharmacology*; D017209:Apoptosis; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism; D002470:Cell Survival; D004396:Coloring Agents / Q000494:pharmacology; D045304:Cytochromes c / Q000378:metabolism; D004249:DNA Damage; D004305:Dose-Response Relationship, Drug; D017930:Genes, Reporter; D006801:Humans; D008156:Luciferases / Q000378:metabolism; D010636:Phenols / Q000494:pharmacology*; D010957:Plasmids / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism*; D013778:Tetrazolium Salts / Q000494:pharmacology; D013844:Thiazoles / Q000494:pharmacology
D000475:Alkenes; D004396:Coloring Agents; D010636:Phenols; D011960:Receptors, Estrogen; D013778:Tetrazolium Salts; D013844:Thiazoles; D045304:Cytochromes c; D008156:Luciferases; D020169:Caspases; C022616:thiazolyl blue; C415745:ascochlorin