Thioredoxin 1 modulates apoptosis induced by bioactive compounds in prostate cancer cells

Abstract

Accumulating evidence suggests that natural bioactive compounds, alone or in combination with traditional chemotherapeutic agents, could be used as potential therapies to fight cancer. In this study, we employed four natural bioactive compounds (curcumin, resveratrol, melatonin, and silibinin) and studied their role in redox control and ability to promote apoptosis in androgen sensitive and insensitive prostate cancer cells. Here is shown that curcumin and resveratrol promote ROS production and induce apoptosis in LNCaP and PC-3. An increase in reactive species is a trigger event in curcumin-induced apoptosis and a consequence of resveratrol effects on other pathways within these cells. Moreover, here we demonstrated that these four compounds affect differently one of the main intracellular redox regulator, the thioredoxin system. Exposure to curcumin and resveratrol promoted TRX1 oxidation and altered its subcellular location. Furthermore, resveratrol diminished TRX1 levels in PC-3 cells and increased the expression of its inhibitor TXNIP. Conversly, melatonin and silibinin only worked as cytostatic agents, reducing ROS levels and showing preventive effects against TRX oxidation. All together, this work explores the effect of compounds currently tested as chemo-preventive agents in prostate cancer therapy, on the TRX1 redox state and function. Our work shows the importance that the TRX system might have within the differences found in their mechanisms of action. These bioactive compounds trigger different responses and affect ROS production and redox systems in prostate cancer cells, suggesting the key role that redox-related pathways might play in processes like differentiation or survival in prostate cancer.

Silibinin Attenuates Silica Dioxide Nanoparticles-Induced Inflammation by Suppressing TXNIP/MAPKs/AP-1 Signaling

“…Silibinin administration markedly declined the phosphorylation of MAPKs and the expression of AP-1 in SiONPs-treated mice. These results were also supported by previous studies [24,25,40], in which silibinin attenuated cigarette smoke-induced pulmonary inflammation by suppressing ERK1/2 and downregulated the expression of MAPK and AP-1 in human lung carcinoma cells. Therefore, these results indicated that the therapeutic effects of silibinin on SiONPs-induced airway inflammation was involved in the suppression of MAPKs phosphorylation.…”

A Mini-Review of Reactive Oxygen Species in Urological Cancer: Correlation with NADPH Oxidases, Angiogenesis, and Apoptosis

“…Actually, numerous studies have shown that the induction of apoptosis by natural products reduced ROS production in prostate cancer cells. Because of space constraints, we introduce only the most recent reports published in 2017; Punica granatum (pomegranate) peel in mouse prostate cancer cells (TRAMP-C1) [ 128 ]; a new nanoemulsion system of rutin in PC-3 [ 129 ]; benzyl isothiocyanate in cruciferous plants in CRW-22Rv1 and PC-3 [ 130 ]; curcumin and resveratrol in LNCaP and PC-3 cells [ 131 ]; Chikusetsu saponin Iva, isolated from Aralia taibaiensis in PC-3 [ 132 ]; chrysin, a natural flavone found in numerous plant extracts, honey, and propolis, in DU145 and PC-3 cells [ 133 ]; lasalocid, an antibiotic from the group of carboxylic ionophores produced by Streptomyces lasaliensis , in PC-3 [ 134 ]; naringenin, an anti-oxidant flavonoid derived from citrus, in PC-3 [ 135 ]; and coumestrol, a major phytoestrogen abundant in soybeans, legumes, Brussels sprouts, and spinach, in LNCaP and PC-3 cells [ 136 ]. Furthermore, treatment with WZ35, a chemical analog of curcumin, induced apoptosis in two prostate cancer cell lines (RM-1 and DU145), and this anti-cancer effect depended on ROS production [ 137 ].…”

An Evaluation of the In Vitro Roles and Mechanisms of Silibinin in Reducing Pyrazinamide- and Isoniazid-Induced Hepatocellular Damage

“…5B). This also coincides with silibinin's ability to increase levels of endogenous proteins that protect cells from oxidative damage, including various mediators along the MAPK pathway (Chen et al, 2006), thioredoxin (Rodriguez-Garcia et al, 2017), and superoxide dismutase (SOD) (Hamza and Al-Harbi, 2015).…”

“…Silibinin is a herbal product derived from milk thistle that has been postulated to protect against liver injury caused by various chemotherapeutic (Patel et al, 2010) and toxic agents (Fanoudi et al, 2018;Jiménez-Arellanes et al, 2016;Ma et al, 2016). Two factors contribute to silibinin's popularity over other chemical drugs in liver disease: it has low toxicity (Flora et al, 1998) and exhibits a broad spectrum of hepatoprotective mechanisms (Polachi et al, 2016;Rodriguez-Garcia et al, 2017;Vargas-Mendoza et al, 2014). Many of silibinin's mechanisms of action can be attributed to its antioxidant, anti-inflammatory, immunomodulatory, and antifibrotic actions (Abenavoli et al, 2018).…”