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새로운 Anthraquinone 유도체, DHAQ-97의 항암작용: 아폽토시스에 의한 인체 유방암세포 사멸 유도
허연진(Yeon-Jin Hurh),김정환(Jung-Hwan Kim),장정희(Jung-Hee Jang),안병준(Byung-Zun Ahn),서영준(Young-Joon Surh) 한국환경성돌연변이발암원학회 2000 한국환경성돌연변이·발암원학회지 Vol.20 No.1
DHAQ-97, (2-(3-[p-bis(2-chloroethyl)aminophenyl]-2-formylaminopropanoyloxy)methyl-1,4-dihydroxy-9,10-anthraquinone), is a novel anthraquinone derivative synthesized for use as an anti-neoplastic agent. In the present study, we have evaluated the selective cytotoxicity of DHAQ-97 by comparing its effects on viability and proliferation of human breast cancer cell line (MCF-7) versus normal immortalized breast epithelial cell line (MCF-10A). Thus, DHAQ-97 reduced both viability and proliferation of MCF-7 cells to a much greater extent than did for MCF-10A cells. The growth inhibitory and anti-proliferative properties of DHAQ-97 appear to be attributable to its ability to induce apoptosis as revealed by positive staining after in situ nick-end labeling<br/> (TUNEL), cleavage of poly(ADP-ribose)polymerase, release of mitochondrial cytochrome c into cytoplasm, and increased expression of pro-apoptotic Bax protein. Recent studies have indicated possible involvement of the ubiquitous eukaryotic transcription factor, NF-kappa B (NF-kB) in the regulation of apoptotic cell death. In line with this notion, the NF-kB inhibitor pyrrolidine dithiocarbamate significantly attenuated the DHAQ-97-induced cytotoxicity in cultured MCF-7 cells. Furthermore, mild activation of NF-kB, as determined by its increased DNA binding capability, was observed 30 min after treatment with 10 μM DHAQ-97. Taken together, the above findings suggest that DHAQ-97 exerts selective cytotoxicity towards cancer cells through induction of<br/> apoptosis, which appears to be regulated by NF-kB.