Protective Effect of Escitalopram on Hepatocellular Carcinoma by Inducing Autophagy.

BACKGROUND: Hepatocellular carcinoma (HCC) is an aggressive cancer with poor prognosis. Although recent research has indicated that selective serotonin reuptake inhibitors (SSRIs), including escitalopram, have anticancer effects, little is known about the effects of escitalopram on HCC. METHODS: Both in vitro and in vivo studies were conducted to verify the potentials of escitalopram on HCC treatment. To explore whether the effects of escitalopram are clinically consistent with laboratory findings, a nationwide population-based cohort study was also adopted to examine the association between escitalopram and HCC risk. RESULTS: As compared with THLE-3 cells, escitalopram significantly inhibited the proliferation of HepG2 and Huh-7 cells. Specifically, escitalopram significantly induced autophagy in HepG2 and Huh-7 cells by increasing the LC3-II/LC3-I ratio and the expression of ATG-3, ATG-5, ATG-7, and Beclin-1 proteins. Moreover, escitalopram significantly inhibited the growth of xenografted Huh-7 cells in SCID mice that were treated with 12.5 mg/kg escitalopram. Accordingly, the risk of HCC was negatively correlated with escitalopram use. CONCLUSIONS: These findings provided evidence supporting the therapeutic potential of escitalopram for HCC. Both laboratory and nationwide population-based cohort evidence demonstrated the attenuated effects of escitalopram on HCC.

Escitalopram oxalate induces apoptosis in U-87MG cells and autophagy in GBM8401 cells.

Glioblastoma multiforme (GBM) is recognized as a most aggressive brain cancer with the worst prognosis and survival time. Owing to the anatomic location of gliomas, surgically removing the tumour is very difficult and avoiding damage to vital brain regions during radiotherapy is impossible. Therefore, therapeutic strategies for malignant glioma must urgently be improved. Recent studies have demonstrated that selective serotonin reuptake inhibitors (SSRIs) have cytotoxic effect on certain cancers. Considering as a more superior SSRI, escitalopram oxalate exhibits favourable tolerability and causes generally mild and temporary adverse events. However, limited information is revealed about the influence of escitalopram oxalate on GBM. Therefore, an attempt was made herein to explore the effects of escitalopram oxalate on GBM. The experimental results revealed that escitalopram oxalate significantly inhibits the proliferation and invasive ability of U-87MG cells and significantly reduced the expressions of cell cycle inhibitors such as Skp2, P57, P21 and P27. Notably, escitalopram oxalate also induced significant apoptotic cascades in U-87MG cells and autophagy in GBM8401 cells. An animal study indicated that escitalopram oxalate inhibits the proliferation of xenografted glioblastoma in BALB/c nude mice. These findings implied that escitalopram oxalate may have potential in treatment of glioblastomas.

Attenuated Effects of Deep-Sea Water on Hepatic Apoptosis in STZ-Induced Diabetic Rats.

Diabetes mellitus (DM) is a metabolic disorder and increasing evidences have indicated a connection between DM and hepatic abnormality. Deep-sea water (DSW) has been applied in many fields, especially in medicine; herein, we investigated the influence of DSW on hepatic apoptosis in streptozocin (STZ)-induced diabetes rats. Our experimental results firstly demonstrated the beneficial effects of 1×DSW, 2×DSW and 3×DSW in alleviating hepatic apoptosis in STZ-induced diabetic rats. We demonstrated that 1×DSW, 2×DSW and 3×DSW significantly suppressed the caspase-3 activity and TUNEL-positive cells in livers of STZ-induced diabetic rats. Significant reductions of both Fas-dependent and mitochondrial-dependent apoptotic molecules were also detected in livers of STZ-induced diabetic rats receiving DSW. Additionally, apoptotic signaling molecules such as phosphorylated IκB-α and NF-κB were significantly reduced in livers of DSW-treated STZ-induced diabetic rats. These findings indicate hepatic protective effects of DSW on DM and suggest DSW as a possible ingredient for health food.

Differential Effects of Wedelia chinensis on Human Glioblastoma Multiforme Cells.

INTRODUCTION: Glioblastoma multiforme (GBM) is the most aggressive glioma, and its diffuse nature makes resection of it difficult. Moreover, even with the administration of postoperative radiotherapy and chemotherapy, prolonged remission is often not achieved. Hence, innovative or alternative treatments for GBM are urgently required. Traditional Chinese herbs and their functional components have long been used in the treatment of various cancers, including GBM. The current study investigated the antitumor activity of Wedelia chinensis and its major functional components, luteolin and apigenin, on GBM. MATERIALS AND METHODS: MTT assay, Transwell migration assay, and flow cytometry analysis were adopted to assess the cell viability, invasive capability, and cell cycle. Immunofluorescence staining and Western blotting were used to detect the expressions of apoptotic and autophagy-related signaling molecules. RESULTS: The W. chinensis extract (WCE) significantly inhibited the proliferation and invasive ability of both GBM8401 and U-87MG cells in a dose-dependent manner. Moreover, differential effects of WCE on GBM8401 and U-87MG cells were observed: WCE induced apoptosis in GBM8401 cells and autophagy in U-87MG cells. Notably, WCE had significant effects in reducing the cell survival and invasive capability of both GBM8401 and U-87MG cells than the combination of luteolin and apigenin. CONCLUSIONS: Taken together, these findings indicate the potential of using WCE and the combination of luteolin and apigenin for GBM treatment. However, further investigations are warranted before considering recommending the clinical use of WCE or the combination of luteolin and apigenin as the standard for GBM treatment.

Effects of taurine on striatal dopamine transporter expression and dopamine uptake in SHR rats.

Dopaminergic deficits in the prefrontal cortex and striatum have been attributed to the pathogenesis of attention-deficit hyperactivity disorder (ADHD). Our recent study revealed that high-dose taurine improves hyperactive behavior and brain-functional signals in SHR rats. This study investigates the effect of taurine on the SHR striatum by detecting the spontaneous alternation, DA transporter (DAT) level, dopamine uptake and brain-derived neurotrophic factor (BDNF) expression. A significant increase in the total arm entries was detected in both WKY and SHR rats fed with low-dose taurine but not in those fed with high-dose taurine. Notably, significantly increased spontaneous alternation was observed in SHR rats fed with high-dose taurine. Significantly higher striatal DAT level was detected in WKY rats fed with low-dose taurine but not in SHR rats, whereas significantly reduced striatal DAT level was detected in SHR rats fed with high-dose taurine but not in WKY rats. Significantly increased dopamine uptake was detected in the striatal synaptosomes of both WKY and SHR rats fed with low-dose taurine. Conversely, significantly reduced dopamine uptake was detected in the striatal synaptosomes of SHR rats fed with high-dose taurine. Accordingly, a negative correlation was detected between striatal dopamine uptake and spontaneous alternation in SHR rats fed with low or high-dose taurine. Significantly increased BDNF was detected in the striatum of both WKY and SHR rats fed with low or high-dose taurine. These findings indicate that different dosages of taurine have opposite effects on striatal DAT expression and dopamine uptake, suggesting high-dose taurine as a possible candidate for ADHD treatment.

Escitalopram oxalate inhibits proliferation and migration and induces apoptosis in non-small cell lung cancer cells.

Population-based cohort studies have revealed that neuroleptic medications are associated with a reduced cancer risk. Recent studies have demonstrated that selective serotonin reuptake inhibitors (SSRIs) have an antiproliferative or cytotoxic effect on certain cancer types. Known as a superior SSRI, escitalopram oxalate exhibits favorable tolerability with generally mild and temporary adverse events. The present study aimed to examine the effects of escitalopram oxalate on non-small cell lung cancer (NSCLC) cells. The experimental results revealed that escitalopram oxalate significantly inhibited the proliferation and invasion of A549, and H460 cells compared with BEAS-2B cells. Additionally, escitalopram oxalate significantly increased the sub-G1 population and caspase-3 activity of A549, and H460 cells. Furthermore, escitalopram oxalate significantly induced mitochondria-dependent apoptotic signaling cascades in A549 and H460 cells, which included increases in the protein expression levels of apoptosis regulator Bax, truncated BH3-interacting domain death agonist, cytochrome c, apoptotic protease-activating factor 1, and cleaved caspase-9. These findings suggest that escitalopram oxalate could serve a therapeutic agent for the treatment of NSCLC due to its antiproliferative and apoptotic effects.

Correction: Effects of taurine on resting-state fMRI activity in spontaneously hypertensive rats.

[This corrects the article DOI: 10.1371/journal.pone.0181122.].

Effects of taurine on resting-state fMRI activity in spontaneously hypertensive rats.

Attention deficit hyperactivity disorder (ADHD) is a global behavior illness among children and adults. To investigate the effects of taurine on resting-state fMRI activity in ADHD, a spontaneously hypertensive rat (SHR) animal model was adopted. Significantly decreased serum C-reactive protein (CRP) was detected in rats of Wistar Kyoto (WKY) high-taurine group and significantly decreased interleukin (IL)-1ß and CRP were detected in rats of SHR low-taurine and high-taurine groups. Moreover, significantly higher horizontal locomotion was detected in rats of WKY low-taurine and SHR low-taurine groups than in those of controls. In contrast, significantly lower horizontal locomotion was detected in rats of the SHR high-taurine group than in those of the SHR control group. Additionally, significantly lower functional connectivity (FC) and mean amplitude of low-frequency fluctuation (mALFF) in the bilateral hippocampus in rats of WKY high-taurine and SHR high-taurine groups was detected. Notably, the mALFF in rats of the SHR low-taurine and high-taurine groups was significantly lower than in those of the SHR control group. These findings suggest that the administration of a high-dose taurine probably improves hyperactive behavior in SHR rats by ameliorating the inflammatory cytokines and modulating brain functional signals in SHR rats.

Lactoferrin Increases Antioxidant Activities and Ameliorates Hepatic Fibrosis in Lupus-Prone Mice Fed with a High-Cholesterol Diet.

Lactoferrin (LF) has beneficial effects against various diseases. However, the effects of LF on liver fibrosis in systematic lupus erythematosus (SLE) are unknown. In this study, NZB/W F1 mice were utilized to investigate the effects of LF on SLE. Experiments reveal that LF significantly increases glutathione and 1,1-diphenyl-2-picryl-hydrazyl levels and significantly decreased malondialdehyde levels in both serum and liver in NZB/W F1 mice. LF also lowered matrix metalloproteinase-9 activity and liver inflammatory indices, such as aminotransferase and alanine aminotransferase. Notably, significantly decreased expression of fibrotic related molecules, including transforming growth factor (TGF)-ß1, tumor necrosis factor-α, interleukin-1ß, and TGF-ß1 receptor, were observed in the livers of NZB/W F1 mice that had been treated with LF. Significantly, suppressed Smad2/3 signaling, α-smooth muscle actin, and collagen deposition were also detected. These findings reveal that LF has beneficial effects on SLE by increasing antioxidant activities and ameliorating liver inflammation and fibrosis, suggesting the therapeutic effectiveness of LF against SLE.

Secondhand smoke induces hepatic apoptosis and fibrosis in hamster fetus.

Secondhand smoke (SHS) is an important health issue worldwide. Inhaling SHS during pregnancy could cause abnormalities in the internal tissues of newborns, which may then impair fetal development and even cause severe intrauterine damage and perinatal death. However, the understanding of cytopathic mechanisms of SHS by maternal passive smoking on fetus liver during pregnancy is still limited. This study analyzed the effects of high-dose SHS (SHSH) on fetus liver using a maternal passive smoking animal model. Experiments showed that hepatic matrix metalloproteinase-9 activity and terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick-end labeling-positive cells were significantly increased in livers from fetuses of hamsters treated with SHSH. Similarly, expressions of both extrinsic and intrinsic apoptotic molecules were significantly higher in livers from fetuses of hamsters exposed to SHSH. Additionally, significantly increased inflammatory proteins, including transforming growth factor ß, inducible nitric oxide synthase, and interleukin 1ß, and fibrotic signaling molecules, including phosphorylated Smad2/3, SP1, and α-smooth muscle actin, were observed in the fetus livers from hamsters treated with SHSH. This study revealed that SHSH not only increased apoptosis through intrinsic and extrinsic pathways in the livers of fetuses from hamsters exposed to SHSH but also augmented hepatic fibrosis via Smad2/3 signaling.