Sodium selenite induces apoptosis via ROS‐mediated NF‐κB signaling and activation of the Bax–caspase‐9–caspase‐3 axis in 4T1 cells

Abstract

Sodium selenite (SSE), a source of inorganic selenium, has been widely used as a clinical cancer treatment, but the precise molecular mechanisms of SSE remain to be elucidated. Our in vitro experiments have confirmed that SSE treatment causes a transient increase in intracellular reactive oxygen species (ROS) levels, resulting in the inhibition of nuclear transcription factor-κB (NF-κB) signaling and p65 and nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha phosphorylation levels in 4T1 cells. The inhibition of NF-κB subsequently increased the expression of the apoptosis gene B-cell lymphoma-2-associated X (Bax) and downregulated the transcription of antiapoptosis genes, such as B-cell lymphoma-2, cellular inhibitor of apoptosis 1, and X-linked inhibitor of apoptosis. Additionally, the accumulation of ROS caused mitochondrial dysfunction, leading to the activation of caspase-9 and -3, thereby resulting in apoptosis. However, modulation of the ROS level by the chemical inhibitor N-acetyl-cysteine reversed these events. Similarly, in vitro murine syngeneic breast tumor models showed that SSE inhibits tumor growth by promoting apoptosis. These results indicate that SSE induces apoptosis via ROS-mediated inhibition of NF-κB signaling and activation of the Bax-caspase-9-caspase-3 axis.

miR‐488 mediates negative regulation of the AKT/NF‐κB pathway by targeting Rac1 in LPS‐induced inflammation

“…They can specifically recognize pathogen‐related molecules, and induce and activate inflammatory factors such as NF‐κB and IFN, and mediate various inflammations such as IL‐1β, IL‐6, and TNF‐α. NF‐κB plays a central role in the transcriptional regulation of much cell‐stimulated cell information, involves in the expression and regulation of various genes, and is a hallmark of activations of cells (Zhang et al, ). In addition, studies have shown that peiminine acts as an anti‐inflammatory agent by inhibiting the activation of the AKT/NF‐κB signaling pathway (Gong, Li, Ma, Guo, & Kan, ).…”

Fabrication and Antitumor Mechanism of a Nanoparticle Drug Delivery System: Graphene Oxide/Chitosan Oligosaccharide/γ‐Polyglutamic Acid Composites for Anticancer Drug Delivery

“…To ascertain the cytotoxicity of the samples, we detected apoptosis by using Annexin V‐FITC and PI as stains . After treatment of Hela cells with different concentrations of GO‐CO‐ γ ‐PGA‐DOX for 24 h, the number of apoptotic cells increased in a concentration dependent manner.…”

Inhibition–Disruption of Candida glabrata Biofilms: Symmetrical Selenoesters as Potential Anti-Biofilm Agents

“…At this stage, the underlying mechanism of action of these novel selenoesters against C. glabrata is unknown and more experiments are needed to determine the ultimate mechanism behind the antifungal activity described herein. Selenocompounds and among them, selenoesters, as briefly mentioned in the introduction [31][32][33][34][35][36][37][38][39], have been proven in previous works to be able to exert a wide range of interesting biological activities, both in the anticancer and The effect of Se-8 on the formation of biofilms generated by C. glabrata dental isolates at t = 0 or 24 h and 4 µg/mL was very weak (0.15 ± 0.03-0.80 ± 0.08 BBU, and 0.07 ± 0.03-0.51 ± 0.14 BBU, respectively), compared to caspofungin (0.93 BBU ± 0.03, 0.56 ± 0.17 BBU, respectively), being statistically significant, p < 0.0001. Selenocompound had the lowest biofilm-reducing effect at 0 and 24 h among the four selenocompounds evaluated in this anti-biofilm assay.…”

“…At this stage, the underlying mechanism of action of these novel selenoesters against C. glabrata is unknown and more experiments are needed to determine the ultimate mechanism behind the antifungal activity described herein. Selenocompounds and among them, selenoesters, as briefly mentioned in the introduction [31][32][33][34][35][36][37][38][39], have been proven in previous works to be able to exert a wide range of interesting biological activities, both in the anticancer and antimicrobial fields; for example, the modulation of the redox cellular state, scavenging of free radicals, increase of the oxidative stress, induction of apoptosis, and inhibition of efflux pumps, among others [31][32][33][34][35][36][37][38][39]. With the caveat that future works would need to prove it, we could hypothesize that one of several of these mechanisms could explain the observed activities for the symmetrical selenoesters presented in this work.…”

“…The mechanisms of action of the selenocompounds are very diverse [34]. In the case of the selenium derivatives with anticancer properties, it has been reported, among other effects, that they can trigger apoptotic events [35], and have the ability to modulate the redox thiolstat thanks to the unique redox properties of this element [36]. Selenium can act, depending on the cellular environment, as an oxidant or a pro-oxidant.…”