Withaferin A sensitizes TRAIL-induced apoptosis through reactive oxygen species-mediated up-regulation of death receptor 5 and down-regulation of c-FLIP

Development of pituitary tumor-transforming gene (PTTG) transgenic mice for the treatment of ovarian cancer.

“…25, 26). This is consistent with previous reports that both Dox and WFA as a monotherapy both produce ROS [156,157,175,178,179,190]. ROS-mediated autophagy has been observed in a number of different carcinoma cell lines [218][219][220].…”

“…Several biological functions have been influenced by WF A including induction of apoptosis through inactivation of Akt and NF-KB [174] as well as decrease of the pro-survival protein Bcl-2 [175,176], G2/M cell cycle arrest [177], and generation of ROS [178,179].…”

“…Bands were quantitated using UN-SCAN-IT software and phospho-proteins compared to relative p-p85S6K412 total protein after p-p70S6K389 normalization with Dox is known to produce ROS as a part of its mechanism [156,157]. There have also been numerous reports about WF A generating ROS production as a part of its apoptotic mechanism in various cancer types [175,178,179,190]. Therefore, we asked whether WFA could enhance the effect of the low concentration of Dox after 24 hr of treatment using the detection agent H 2 DCFDA, which is a stable non -polar compound that is readily diffused into the 54 cells.…”

Combination of withaferin A and X-ray irradiation enhances apoptosis in U937 cells

“…Several studies have been reported for its anti-tumor effects, including the inhibitory activities of tumor cell growth, angiogenesis and metastasis (Stan et al, 2008a;Mohan et al, 2004). Recently, a variety of biological roles of Wit A have been reported; induction of apoptosis by ROS generation (Malik et al, 2007;Lee et al, 2009), anti-proliferative effect of Wit A by G2/ M phase cell cycle arrest (Stan et al, 2008b), inhibition of cell adhesion molecules by inactivation of Akt and NF-jB (Oh and Kwon, 2009), and inhibition of cell migration/invasion through down-regulation of signal transducer and activator of transcription 3 (STAT3) activation in human breast cancer cells (Lee et al, 2010). However, the detailed molecular mechanisms by which Wit A contributes to cancer cell death have not yet been fully understood.…”

Acrolein sensitizes human renal cancer Caki cells to TRAIL-induced apoptosis via ROS-mediated up-regulation of death receptor-5 (DR5) and down-regulation of Bcl-2

“…Recently we reported that endoplasmic reticulum (ER) stress-induced CHOP transcriptional factor plays a critical role in DR5 induction [27,28]. Thus, we next examined whether acrolein alters the levels of ER stress-related proteins.…”