Induction of Apoptosis by Yomogin in Human Promyelocytic Leukemic HL-60 Cells

Abstract

Yomogin is an active compound isolated from Artemisia princep, a traditional Oriental medicinal herb, which has been shown to inhibit tumor cell proliferation. In this study, we investigated the effects of yomogin on the cytotoxicity, induction of apoptosis, and putative pathways of its actions in human promyelocytic leukemia cells. Yomogin-treated HL-60 cells displayed several features of apoptosis, including DNA fragmentation, formation of DNA ladders in agarose gel electrophoresis, and externalization of annexin-V targeted phosphatidylserine residues. We observed that yomogin caused activation of caspase-8, caspase-9, and caspase-3. A general caspase inhibitor (z-VAD-fmk), caspase-8 inhibitor (z-IETD-fmk) and caspase-3 inhibitor (z-DEVD-fmk), almost completely suppressed the yomogin-induced DNA fragmentation. We further demonstrated that yomogin induced Bid cleavage, mitochondrial translocation of Bax from the cytosol, and cytochrome c release from mitochondria in a caspase-8-dependent manner. Taken together, our data indicate that yomogin is a potent inducer of apoptosis and facilitates its activity via caspase-8 activation, Bid cleavage, Bax translocation to mitochondria, and subsequent release of cytochrome c into the cytoplasm, providing a potential mechanism for the anticancer activity of yomogin.

Antiproliferative effects of extracts from IranianArtemisiaspecies on cancer cell lines

“…Its smoke and water-soluble extracts induce apoptosis via the mitochondrial pathway in breast cancer cells (Sarath et al, 2007). Yomogin is an active compound isolated from A. princeps, a traditional oriental medicinal herb, which has been shown to inhibit the proliferation of human promyelocytic leukemia cells through the induction of apoptosis (Jeong et al, 2004). Aqueous and methanol herbal extracts from A. capillaries and A. annua L. showed inhibitory activity against different cancer cell lines (Sun et al, 2007).…”

Sesquiterpene Lactones fromArtemisiaGenus: Biological Activities and Methods of Analysis

“…So, these combinations can be used in therapy of myeloid leukemias [ 40 ]. Moreover, yomogin induces apoptosis in human promyelocytic leukemia HL-60 cells through caspase-8 activation, Bid cleavage, and Bax translocation to mitochondria, followed by release of cytochrome c into the cytoplasm [ 41 ].…”

Actions of Artemisia vulgaris extracts and isolated sesquiterpene lactones against receptors mediating contraction of guinea pig ileum and trachea

“…Previously, both of these compounds were also isolated from the chloroform partition of the aqueous extract from the same plant variety (Tigno et al, 2000). Yomogin has also been reported to be present in other species of Artemisia (Geissman, 1966;Nagaki, 1984;Jeong et al, 2004) and is known for its anti-carcinogenic properties (Zhang et al, 2005). Previous reports have shown that the anti-inflammatory properties of yomogin and similar sesquiterpene lactones from a variety of medicinal plants are due to inhibition of nitric oxide production in lipopolysaccharide-activated macrophages (Ryu et al, 1998;Dirsch et al, 2000;Zhang et al, 2005).…”