Diarylheptanoid hirsutenone enhances apoptotic effect of TRAIL on epithelial ovarian carcinoma cell lines via activation of death receptor and mitochondrial pathway

Abstract

Tumor necrosis factor (TNF)-related apoptosis inducing ligand (TRAIL) induces apoptosis in various cancer cells. Diarylheptanoids such as hirsutenone and oregonin have been shown to have anti-inflammatory and anti-tumor effects. However, it is still unknown by which mechanism diarylheptanoids induce cell death. In addition, the effect of hirsutenone on TRAIL-induced apoptosis in the human epithelial ovarian carcinoma cell lines is unknown. To assess the apoptosis promoting effect of hirsutenone, we investigated the effect of hirsutenone on the apoptotic effect of TRAIL using the human epithelial carcinoma cell lines OVCAR-3 and SK-OV-3. TRAIL induced nuclear damage, decrease in Bid, Bcl-2 and Bcl-xL protein levels, increase in Bax levels, loss of the mitochondrial transmembrane potential, cytochrome c release, activation of caspases (8, 9 and 3) and increase in tumor suppressor p53 levels. Hirsutenone enhanced the TRAIL-induced apoptosis-related protein activation, nuclear damage and cell death. The results suggest that hirsutenone may enhance the apoptotic effect of TRAIL on ovarian carcinoma cell lines by increasing the activation of the caspase-8- and Bid-dependent pathways and the mitochondria-mediated apoptotic pathway, leading to caspase activation. Hirsutenone may confer a benefit in the TRAIL treatment of epithelial ovarian adenocarcinoma.

Diarylheptanoid Hirsutenone Attenuates Osteoclastogenesis by Suppressing IFNγ and NF-κB Signaling in Th1 and Preosteoclastic Cells

“…Cumulative evidences suggest that HTN has bioactive properties as a diarylheptanoid and plays a key role in inducing tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-dependent apoptosis and in the inhibition of T cell-dependent cytokines, such as IL-2, 4, 5, 10, 13, and IFNγ. [13][14][15] We further demonstrated that HTN inhibited IFNγ-related gene expression in mouse splenocytes. Therefore, in this study, we investigated whether HTN effectively inhibits osteoclastogenesis by blocking the expression of T cell-mediated cytokines via indirectly the inactivation of T cells or directly attenuating osteoclastogenesis, thus indicating potential therapeutic advantages for bone resorption.…”

The Diarylheptanoid Hirsutenone Sensitizes Chemoresistant Ovarian Cancer Cells to Cisplatin via Modulation of Apoptosis-inducing Factor and X-linked Inhibitor of Apoptosis

“…Rakesh Goel and Barbara Vanderhyden (Ottawa Hospital Cancer Center, Ottawa, ON, Canada) and cultured previously as reported (19, 20). OV2008 and C13 cells were cultured in RPMI, whereas OVCAR-433, A2780s, A2780cp, Hey, Occ-1, SKOV3, and OVCAR-432 were cultured in DMEM, supplemented with 10% FBS.…”

“…sibirica (17). Evidence suggests that hirsutenone exhibits numerous bioactive properties, including the ability to suppress T cell activation and induce TRAIL-dependent apoptosis (18, 19). However, the effect of hirsutenone on CDDP sensitivity in cancer cells has not previously been investigated.…”

Structure- and isoform-specific glucuronidation of six curcumin analogs

“…Galangal, the rhizome of Alpinia officinarum Hance (Zingiberaae), is a spice widely used in Europe and China for over 1000 years. Phytochemical studies of this medicinal plant have led to the isolation of many diarylheptanoids (curcumin analogs) that possess diverse pharmacological effects such as antiemetic (Shin et al, 2002;Yang et al, 2002), anti-inflammatory (Li et al, 2011;Matsuda et al, 2006), anti-tumor (Chen et al, 2015;Lee et al, 2012;Matsuda et al, 2009), and anti-oxidant activities (Kose et al, 2015;Riethmuller et al, 2015).…”