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

Abstract

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 (DeltaPsi(m)), 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 DeltaPsi(m) 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 DeltaPsi(m).

Characteristic Features of Cytotoxic Activity of Flavonoids on Human Cervical Cancer Cells

“…Cisplatin is one of the most potent and widely used chemotherapeutic drugs for treatment of various solid tumors including cervical cancers; however, chemoresistance to this drug has remained a major limitation of cisplatin-based chemotherapy (Chung et al, 2010;He et al, 2012;Singh et al, 2013). Combination of cisplatin with other agents can be a promising strategy to overcome resistance and natural flavonoids may hold a great potential in such sensitization.…”

Chemopreventive effects of standardized ethanol extract from the aerial parts of Artemisia princeps Pampanini cv. Sajabal via NF-κB inactivation on colitis-associated colon tumorigenesis in mice

“…In addition, the flavonoids (eupatilin, jaceosidin, and eupafolin) isolated from EAPP have been previously shown to have anti-proliferative effects on cancer cells via the inductions of cell cycle arrest and apoptosis (Chung et al, 2010;Hosokawa et al, 1992). HPLC was used to identify flavonoids in EAPP and the HPLC/UV chromatogram obtained ( Supplementary Fig.…”

“…Sajabal induces apoptosis via mitochondrial pathway in human cervical cancer HeLa cells (Ju et al, 2012) and Artemisia leaf extract also induces apoptosis in human endometriotic cells through regulation of the p38 and NF-κB pathways . Its flavonoid components, such as, eupatilin, jaceosidin, and eupafolin, induce G2/M cell cycle arrest and apoptosis via the caspase-and mitochondrial-dependent pathway and the inactivation of NF-κB pathways in human endometrial and cervical cancer cells (Cho et al, 2011;Chung et al, 2010;Lee et al, 2013). However, no report has been issued on the detailed in vivo and in vitro biological efficacies and involved the underlying molecular mechanism of EAPP in human colon cancer.…”

Effect of isosecotanapartholide isolated from Artemisia princeps Pampanini on IL-33 production and STAT-1 activation in HaCaT keratinocytes

“…ISTP, isolated from Artermisia rutifolia and Artermisia iwayomogi, has a sesquiterpene lactone structure and has been demonstrated to inhibit nitric oxide synthase. The present study investigated whether APE contained other primary compounds, including ISTP, eupatilin (24) and jaceosidin (25). Compounds were extracted from APE by HPLC and various other peaks were detected (Fig.…”