Eupafolin, a flavonoid isolated from Artemisia princeps, induced apoptosis in human cervical adenocarcinoma HeLa cells

• Published in: Molecular nutrition & food research 2010-09, Vol.54 (9), p.1318-1328
• Main Authors: Chung, Kyung-Sook, Choi, Jung-Hye, Back, Nam-In, Choi, Myung-Sook, Kang, Eun-Kyung, Chung, Hae-Gon, Jeong, Tae-Sook, Lee, Kyung-Tae
• Format: Article
• Language: English
• Subjects: Adenocarcinoma; Adenocarcinoma - drug therapy; Adenosine diphosphate; Annexin V; Antineoplastic Agents, Phytogenic - chemistry; Antineoplastic Agents, Phytogenic - isolation & purification; Antineoplastic Agents, Phytogenic - pharmacology; Apoptosis; Apoptosis - drug effects; Artemisia - chemistry; Artemisia princeps; Bcl-2; Biological and medical sciences; Caspase; Caspases - metabolism; Cell Line, Tumor; Cervical carcinoma; Cervix; Cytochrome; Cytochrome c; Cytochromes; Cytosol; Deoxyribonucleic acid; DNA; DNA fragmentation; DNA Fragmentation - drug effects; Down-Regulation - drug effects; Enzyme Activation - drug effects; Eupafolin; Female; Flavones - chemistry; Flavones - isolation & purification; Flavones - pharmacology; Food industries; Fundamental and applied biological sciences. Psychology; HeLa Cells; Humans; Inhibitory Concentration 50; Kinetics; Lymphocytes B; Lymphoma; Membrane potential; Membrane Potential, Mitochondrial - drug effects; Mitochondria; Mitochondria - drug effects; Mitochondria - enzymology; Mode of action; Permeability - drug effects; Proteins; Proto-Oncogene Proteins c-bcl-2 - genetics; Proto-Oncogene Proteins c-bcl-2 - metabolism; Ribose; Substrates; Uterine Cervical Neoplasms - drug therapy
• ISSN: 1613-4125; 1613-4133
• DOI: 10.1002/mnfr.200900305

Although eupafolin, a flavone found in Artemisia princeps Pampanini, has been shown to inhibit the growth of several human cancer cells, its mode of action is poorly understood. In this study, we investigated the pro-apoptotic activities of eupafolin in human cervical carcinoma HeLa cells. It was found that eupafolin induced apoptosis in a dose-dependent manner, as evidenced by DNA fragmentation and the accumulation of positive cells for annexin V. In addition, eupafolin triggered the activations of caspases-3, -6, -7, -8, and -9 and the cleavages of their substrates, such as, poly (ADP-ribose) polymerase and lamin A/C. Furthermore, treatment with eupafolin resulted in a loss of mitochondrial membrane potential (ΔΨm), increased the release of cytochrome c to the cytosol, and altered the expression levels of B-cell lymphoma 2 (Bcl-2) family proteins. Interestingly, caspase-8, an initiator caspase, was activated after the loss of ΔΨm and the activations of caspases-3 and -9. Moreover, treatment with z-DEVD-fmk (a specific caspase-3 inhibitor) and the overexpression of Bcl-2 prevented eupafolin-stimulated caspase-8 activation. Altogether, these results suggest that the eupafolin-induced apoptosis in HeLa cells is mediated by caspase-dependent pathways, involving caspases-3, -9, and -8, which are initiated by the Bcl-2-dependent loss of ΔΨm.