Reactive oxygen species up‐regulate p53 and Puma; a possible mechanism for apoptosis during combined treatment with TRAIL and wogonin

Abstract

Background and purpose: Tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) triggers apoptotic death in a variety of cancer cells without marked toxicity to most normal cells. We previously reported that wogonin, a potent anticancer agent from a Chinese herb, up-regulates p53 in prostate cancer cells. In this study, the effects of combinations of TRAIL and wogonin on a human prostate cancer cell line LNCaP, resistant to TRAIL, was evaluated for evidence of synergy in triggering apoptosis. Experimental approach: Western blot assay and the 'comet' assay were used to study the underlying mechanisms of cell death and search for any mechanisms of enhancement of TRAIL-induced apoptosis in the presence of wogonin. Key results: During combined treatment with wogonin and TRAIL, cytotoxicity, poly(ADP-ribose) polymerase cleavage and caspase activation were associated with up-regulation of p53 through DNA damage and reactive oxygen species (ROS) generation. N-acetylcysteine (NAC), an antioxidant, inhibited ROS generation and synergistic interaction between TRAIL and wogonin. Experimental results in human colon cancer HCT116 cells demonstrated that p53-dependent Puma up-regulation played an important role; deficiency in either p53 or Puma prevented wogonin-enhanced TRAIL-induced apoptosis. Conclusions and implications:The present studies suggest that wogonin enhances TRAIL-induced cytotoxicity through up-regulation of p53 and Puma, mediated by ROS.

FOXO1 silence aggravates oxidative stress-promoted apoptosis in cardiomyocytes by reducing autophagy

“…It has been well recognized that overproduced ROS in oxidative stress reduce cell viability and induce apoptosis (Lee et al, 2009;Chandra et al, 2000). In the present study, we confirmed the apoptosis induction by hydrogen peroxide in cardiomyocyte H9c2 cells, significantly higher level of apoptotic H9c2 cells, higher levels of activated caspase 3 (cleaved caspase 3) and more lyzed PARP by the active caspase 3 were induced in the hydrogen peroxide (H 2 O 2 ) group, compared to the control group.…”

“…Cardiac oxidative injury during I/R causes damage to cardiomyocytes or even results in cell death followed by such physic-pathological processes (Murphy and Steenbergen, 2008) as fibrosis, hypertrophy, and ventricular chamber dilation, and ultimately leads to heart failure (Finkel and Holbrook, 2000;Vanden Hoek et al, 1997;Becker et al, 1999). Overloaded reactive oxygen species (ROS) such as superoxide anions, hydrogen peroxide and hydroxyl radicals in oxidative stress deregulate the stress-signaling pathways, and can compromise cell viability and trigger apoptosis (Lee et al, 2009;Chandra et al, 2000), by inducing damage to DNA, protein and lipids (Martindale and Holbrook, 2002). On the other hand, there are multiple markers exerting protective roles against the ROS-mediated cardiac injury, including AMP-activated protein kinase (AMPK), sirtuins (Sirts) (Alcendor et al, 2007;Wang et al, 2009) and the activated phosphoinositide 3-kinase/AKT (PI3K/AKT) signaling (Chen et al, 2013).…”

Phytochemicals: cancer chemoprevention and suppression of tumor onset and metastasis

“…Benzyl isothiocyanate (BITC), a component of cruciferous vegetables, has also been reported to be able to sensitize pancreatic adenocarcinoma cells to TRAIL and activate both extrinsic and intrinsic apoptotic pathways [104]. Wogonin, a component from Scutellaria baicalensis, also enhances TRAIL-induced cytotoxicity in LNcaP cells [105].…”

Combining naturally occurring polyphenols with TNF-related apoptosis-inducing ligand: a promising approach to kill resistant cancer cells?

“…This amplification loop is negatively controlled by anti-apoptotic members of the Bcl-2 family and is heavily dependent on Bax [30], in type II cells [31]. TRAIL-induced apoptosis can also be negatively regulated by other intracellular factors including cellular inhibitor of apoptosis protein (cIAP), X-linked IAP (XIAP) or survivin, downstream of Methyldihydroquercetin BB-1 [70] Kaempferol [71,73] Myricetin [74] Flavanones ND Flavones Apigenin [75,76] Luteolin [77,78] Wogonin [79,80,82] Baicalein [84] Flavopyridol (semi-synthetic flavone) [125][126][127][128][129][130] Isoflavones Genistein [86][87][88][89][90][91][92] Daidzein [93] Chalcones…”

“…Wogonin was shown to inhibit TNF-a-induced NFjB activation in a ROS-independent manner, but it was not confirmed for TRAIL. More recently, Lee et al [80] underlined the importance of P53, Puma, and Bax during co-treatment with TRAIL and wogonin, using prostate and colon carcinomas deficient for each of these proteins. A schematic model of action was proposed, where wogonin induced ROS production and subsequent P53 activation.…”