Advances in understanding the role of dendritic cells in aplastic anaemia.

Aplastic anaemia (AA) is an autoimmune disease characterized by haematopoietic failure in the bone marrow. Abnormal activation and hyperfunction of T lymphocytes are believed to cause bone marrow damage, which plays a major role in AA pathogenesis. Dendritic cells (DCs) play a vital role in the immune system by processing antigens for presentation to T cells and regulating their differentiation and function. DC dysfunction may cause abnormal T-cell activation. Recent studies have associated the occurrence and development of AA with DC function. In this review, we have discussed the role of DCs in AA pathogenesis and their potential as putative therapeutic targets for AA.

Microenvironment derived from metanephros transplantation inhibits the progression of acute kidney injury in glycerol-induced rat models.

Background: Embryonic metanephros is the mammalian renal anlagen, which is considered as a potential source for the regeneration of functional whole kidneys. Some studies reported that metanephros implanted into unilateral nephrectomized animals can develop into kidney tissue. However, kidneys are nephrotoxic in renal failure patients, and whether metanephros can grow in nephrotoxic has not been reported. This study aims to investigate the growth of metanephros in acute nephrotoxic environment and analyze the therapeutic effect of metanephros microenvironment on acute kidney injury (AKI).Methods: AKI was induced in 200 g Wistar rats by giving intramuscular injections of 50% glycerol (10 mL/kg) in their hind limbs. 45 rats were divided randomly into three groups (control, glycerin, and metanephros). Metanephros group was transplanted two metanephroi (embryonic day 15) into the renal capsule of AKI rats. Glycerin group was AKI rats without transplantation. Control group was untreated.Results: Mature glomeruli and tubules were detected in the grafts in metanephros group, which means that metanephroi can grow into tissues with mature kidney structure under acute nephrotoxic. Then, we assessed the renal function of host rats and found that there were fewer tubular necrosis in metanephros group than glycerin group, and the serum creatinine and urea nitrogen were significantly lower in metanephros group than glycerin group.Conclusion: These results suggested that embryonic metanephroi can grow into tissues with mature kidney structure under acute nephrotoxic, and the graft microenvironment was effective in inhibiting the progression of AKI, which provides a new approach for the treatment of acute renal injury.

Bisbibenzyls, novel proteasome inhibitors, suppress androgen receptor transcriptional activity and expression accompanied by activation of autophagy in prostate cancer LNCaP cells.

CONTEXT: Bisbibenzyl compounds have gained our interests for their potential antitumor activity in malignant cell-types. OBJECTIVE: The objective of this study is to investigate the effect of bisbibenzyl compounds riccardin C (RC), marchantin M (MM), and riccardin D (RD) on androgen receptor (AR) in prostate cancer (PCa) cells. MATERIALS AND METHODS: After exposure to 10 µM of the compounds for 24 h, cell cycle and cell survival analyses were performed using FACS and MTT assay to confirm the effect of these bisbibenzyls on PCa LNCaP cells. Changes in the AR expression and function, as the result of exposure to the compounds, were investigated using real-time PCR, ELISA, transient transfection, western blotting (WB), immunoprecipitation, and immunofluorescence staining (IF). Chemical-induced autophagy was examined by WB, IF, and RNAi. RESULTS: RC, MM, and RD reduced the viability of LNCaP cells accompanied with arrested cell cycle in the G0/G1 phase and induction of apoptosis. Further investigation revealed that these compounds significantly inhibited AR expression at mRNA and protein levels, leading to the suppression of AR transcriptional activity. Moreover, inhibition of proteasome activity by bisbibenzyls, which in turn caused the induction of autophagy, as noted by induction of LC3B expression, conversion, and accumulation of punctate dots in treated cells. Co-localization of AR/LC3B and AR/Ub suggested that autophagy contributed to the degradation of polyubiquitinated-AR when proteasome activity was suppressed by the bisbibenzyls. DISCUSSION AND CONCLUSION: Suppression of proteasome activity and induction of autophagy were involved in bisbibenzyl-mediated modulation of AR activities and apoptosis, suggesting their potential in treating PCa.

Establishment of an induced pluripotent stem cell line from a patient with X-linked Alport syndrome carrying a hemizygous splicing variant (NM_033380; c.929[exon 16]delG) in the collagen type IV alpha 5 chain gene.

X-linked hereditary Alport syndrome (XLAS) type 1 (OMIM: 301050) results from a pathogenic variant in the collagen type IV alpha 5 chain (COL4A5) gene.A human induced pluripotent stem cell (iPSC) line was generated from peripheral blood mononuclear cells of a 7-year-old male patient with XLAS using non-integrating episomal vector technique. The male donor had a heterozygous variant in the COL4A5 gene. The resulting iPSC line has a standard karyotype, can express pluripotent biomarkers, and is able to create germ layers in vivo. It can serve as a valuable cellular model for investigating the underlying mechanisms of XLAS.

DIA proteomics analysis reveals the mechanism of folic acid-induced acute kidney injury and the effects of icariin.

The complexities of acute kidney injury (AKI), a multifaceted pathological occurrence, are not fully understood. At present, there is a lack of effective pharmaceutical treatments in clinical practice. Studies have shown that icariin has beneficial effects in models of acute kidney injury (AKI) caused by cisplatin and lipopolysaccharide (LPS). The aim is to explore the mechanisms that cause folic acid (FA)-induced AKI and examine the protective effects of icariin against this condition. To establish a mouse model of AKI, FA was administered via intraperitoneal injection. Icariin was used as the drug intervention. The model and the impact of drug intervention were assessed using measurements of renal function parameters, staining with hematoxylin and eosin, and Q-PCR. The analysis of protein expression changes in the control, model, and icariin treatment groups was conducted using proteomics. KEGG signaling pathway analysis indicates that differential expressed proteins are enriched in the component and coagulation cascades signaling pathway. Through protein-protein interaction network analysis, it was found that compared to the normal group, the expression of Fibrinogen and other proteins was significantly upregulated at the center of the protein interaction network in the model group. After drug treatment, the expression of these proteins was significantly downregulated. The validation experiment supports the above results. In conclusion, this study clarified the molecular mechanism of FA induced acute renal injury from the proteomics level, and provided target selection for AKI; At the same time, the mechanism of icariin in the treatment of AKI was analyzed from the proteomics level.

Advances in understanding of dendritic cell in the pathogenesis of acute kidney injury.

Acute kidney injury (AKI) is characterized by a rapid decline in renal function and is associated with a high morbidity and mortality rate. At present, the underlying mechanisms of AKI remain incompletely understood. Immune disorder is a prominent feature of AKI, and dendritic cells (DCs) play a pivotal role in orchestrating both innate and adaptive immune responses, including the induction of protective proinflammatory and tolerogenic immune reactions. Emerging evidence suggests that DCs play a critical role in the initiation and development of AKI. This paper aimed to conduct a comprehensive review and analysis of the role of DCs in the progression of AKI and elucidate the underlying molecular mechanism. The ultimate objective was to offer valuable insights and guidance for the treatment of AKI.

Traditional Chinese Medicine and renal regeneration: experimental evidence and future perspectives.

Repair of acute kidney injury (AKI) is a typical example of renal regeneration. AKI is characterized by tubular cell death, peritubular capillary (PTC) thinning, and immune system activation. After renal tubule injury, resident renal progenitor cells, or renal tubule dedifferentiation, give rise to renal progenitor cells and repair the damaged renal tubule through proliferation and differentiation. Mesenchymal stem cells (MSCs) also play an important role in renal tubular repair. AKI leads to sparse PTC, affecting the supply of nutrients and oxygen and indirectly aggravating AKI. Therefore, repairing PTC is important for the prognosis of AKI. The activation of the immune system is conducive for the body to clear the necrotic cells and debris generated by AKI; however, if the immune activation is too strong or lengthy, it will cause damage to renal tubule cells or inhibit their repair. Macrophages have been shown to play an important role in the repair of kidney injury. Traditional Chinese medicine (TCM) has unique advantages in the treatment of AKI and a series of studies have been conducted on the topic in recent years. Herein, the role of TCM in promoting the repair of renal injury and its molecular mechanism is discussed from three perspectives: repair of renal tubular epithelial cells, repair of PTC, and regulation of macrophages to provide a reference for the treatment and mechanistic research of AKI.

Maturation of Nephrons by Implanting hPSC-derived Kidney Progenitors Under Kidney Capsules of Unilaterally Nephrectomized Mice.

BACKGROUND: Human pluripotent stem cell (hPSC)-derived kidney organoids may contribute to disease modeling and the generation of kidney replacement tissues. However, the realization of such applications requires the induction of hPSCs into functional mature organoids. One of the key questions for this process is whether a specific vascular system exists for nephrogenesis. Our previous study showed that short-term (2 weeks) implantation of hPSC-derived organoids below the kidney capsules of unilaterally nephrectomized and immunodeficient mice resulted in the enlargement of organoids and production of vascular cells, although signs of maturation were lacking. METHODS: Organoids were induced for 15 days in vitro and then grafted below kidney capsules of the same unilaterally nephrectomized immunodeficient mouse model to examine whether medium-term (4 weeks) implantation could improve organoid maturation and vascularization, as evaluated by immunofluorescence and transmission electron microscopy. RESULTS: We demonstrated that after 2-4 weeks of implantation, renal organoids formed host-derived vascularization and matured without any exogenous vascular endothelial growth factor. Glomerular filtration barrier maturation was evidenced by glomerular basement membrane deposition, perforated glomerular endothelial cell development, and apical, basal podocyte polarization. A polarized monolayer epithelium and extensive brush border were also observed for tubular epithelial cells. CONCLUSIONS: Our results indicate that the in vivo microenvironment is important for the maturation of human kidney organoids. Stromal expansion and a reduction of nephron structures were observed following longer-term (12 weeks) implantation, suggesting effects on off-target cells during the induction process. Accordingly, induction efficiency and transplantation models should be improved in the future.

Expression of Ezrin and phosphorylated Ezrin (pEzrin) in pancreatic ductal adenocarcinoma.

It has been suggested that ezrin activation plays a key role in the regulation of cancer metastasis. In this study, we immunohistochemically investigated the expression patterns of total ezrin and its two phosphorylated forms, pEzrin(- Thr567) and pEzrin(- Tyr353), in 66 samples of invasive pancreatic carcinomas and 11 samples of normal pancreas tissues. Positive expressions of ezrin and pEzrin(- Thr567) were detected in most PDAC tissues, significantly higher than that of pEzrin(- Tyr353). Furthermore, overexpression of pEzrin(- Tyr353) in pancreatic cancers was associated with positive lymph node metastasis, less differentiation, pAkt overexpression, and shorter survival times. pEzrin(- Tyr353) may be a potent prognosis predictor for pancreatic cancer.

In vitro induction and in vivo engraftment of kidney organoids derived from human pluripotent stem cells.

The shortage of transplantable organs impedes the development of tissue-engineered alternatives. Producing tissues similar to immature kidneys from pluripotent stem cells is possible in vitro, but the size of the organoids is limited. Furthermore, in vivo implantation is necessary for organoid development and functional maturation. In the present study, the induction procedure was optimized and kidney organoids derived from induced pluripotent stem cells in vitro were produced. The kidney organoids were examined by immunofluorescence and quantitative PCR. Then, a unilateral nephrectomy model was established that was beneficial to the compensatory proliferation of the other kidney. Finally, these organoids were implanted below the kidney capsules of immunodeficient mouse hosts that had been nephrectomized unilaterally. This implantation resulted in the enlargement of the organoids and the production of vascular cells. Although signs of organoid maturation were lacking in short-term culture in vivo, the present study provided a method for studying kidney organoid development in vivo.

Paris polyphylla ethanol extract induces G2/M arrest and suppresses migration and invasion in bladder cancer.

BACKGROUND: Paris polyphylla is a traditional Chinese medicinal herb with multiple antitumor activities, but the role of P. polyphylla in bladder cancer (BC) is under investigation. This study aims to examine the antitumor activities of P. polyphylla ethanol extract (PPE) on BC cells and elucidate the underlying mechanisms. METHODS: Viable cells were counted using the trypan blue exclusion assay. The cell cycle was analyzed using flow cytometry, and scratch wound-healing and transwell assays were used to evaluate cell migration and invasion abilities, respectively. The protein expression levels were determined by western blotting. A xenograft model was used to assess the in vivo inhibitory effect of PPE on BC tumor growth. RESULTS: Our results showed that PPE inhibited the growth of BC cells in vivo and in vitro. Mechanistically, PPE regulated the levels of cell cycle-associated proteins, with PPE-induced G2/M phase arrest occurring through cyclin-dependent kinase inhibitor 1 (CDKN1A) accumulation and cyclin B1 (CCNB1)/cyclin-dependent kinase 1 (CDK1) inhibition. BC tumor growth was also inhibited by PPE treatment. Moreover, the migration and invasion abilities of J82 cells were suppressed through modulating epithelial-mesenchymal transition (EMT) regulatory factors with upregulation of cadherin-1 (CDH1) and downregulation of cadherin-2 (CDH2), snail family transcriptional repressor 2 (SNAI2), and twist family bHLH transcription factor 1 (TWIST1). CONCLUSIONS: PPE inhibited cell growth, induced G2/M arrest, and suppressed the migration and invasion of J82 cells. BC tumor growth in vivo was also inhibited by PPE. Our results lay the foundation for further studies on the antitumor mechanisms of PPE.

Proteomic and tissue array profiling identifies elevated hypoxia-regulated proteins in pancreatic ductal adenocarcinoma.

We identified a group of hypoxia-regulated proteins upregulated in microdissected pancreatic cancer nests compared with normal pancreatic ducts. Immunohistochemical study further validated that pancreatic cancers had significantly higher expression levels of glucose-regulated protein 78, macrophage migration inhibitory factor and annexin A5 than normal pancreas tissues, these protein biomarkers also demonstrated high receiver operating characteristic curves in discriminating pancreatic cancers from normal pancreas. In conclusion, our study indicated a link between pancreatic cancer and hypoxia-regulated proteins. Glucose-regulated protein 78, macrophage migration inhibitory factor and annexin A5 might be promising targets for pancreatic cancer diagnosis and therapy.

Polyphyllin I induces cell cycle arrest in prostate cancer cells via the upregulation of IL6 and P21 expression.

BACKGROUND: Polyphyllin I has been reported to possess anticancer properties in various cancer types, including prostate cancer. However, little is known about the potential of Polyphyllin I in induction of prostate cancer cell cycle arrest and its underlying mechanisms. METHODS: The anti-proliferation activity of Polyphyllin I was tested using cell counting kit-8 assay. The cell cycle arrest effects of Polyphyllin I were confirmed by flow cytometry. Western blot was used to test the effect of Polyphyllin I on cell cycle-related protein expression. Reverse transcription-polymerase chain reaction was used to test the expression of genes regulating P21 expression. RESULTS: Polyphyllin I induced prostate cancer cell cycle arrest in G0/G1 phase in concentration-dependent manner. Polyphyllin I induced cell cycle arrest by upregulating the expression of P21. Further studies showed that the upregulation of p21 expression induced by Polyphyllin I via the upregulation of IL6 expression. CONCLUSION: Polyphyllin I could induce cell cycle arrest in G0/G1 phase in prostate cancer cells by upregulating the expression of P21 and IL6.

Induced Intermediate Mesoderm Combined with Decellularized Kidney Scaffolds for Functional Engineering Kidney.

Background: Chronic kidney disease is a severe threat to human health with no ideal treatment strategy. Mature mammalian kidneys have a fixed number of nephrons, and regeneration is difficult once they are damaged. For this reason, developing an efficient approach to achieve kidney regeneration is necessary. The technology of the combination of decellularized kidney scaffolds with stem cells has emerged as a new strategy; however, in previous studies, the differentiation of stem cells in decellularized scaffolds was insufficient for functional kidney regeneration, and many problems remain. Methods: We used 0.5% sodium dodecyl sulfate (SDS) to produce rat kidney decellularized scaffolds, and induce adipose-derived stem cells (ADSCs) into intermediate mesoderm by adding Wnt agonist CHIR99021 and FGF9 in vitro. The characteristics of decellularized scaffolds and intermediate mesoderm induced from adipose-derived stem cells were identified. The scaffolds were recellularized with ADSCs and intermediate mesoderm cells through the renal artery and ureter. After cocultured for 10 days, cells adhesion and differentiation was evaluated. Results: Intermediate mesoderm cells were successfully induced from ADSCs and identified by immunofluorescence and Western blotting assays (OSR1 + , PAX2 +). Immunofluorescence showed that intermediate mesoderm cells differentiated into tubular-like (E-CAD + , GATA3 +) and podocyte-like (WT1 +) cells with higher differentiation efficiency than ADSCs in the decellularized scaffolds. Comparatively, this phenomenon was not observed in induced intermediate mesoderm cells cultured in vitro. Conclusion: In this study, we demonstrated that intermediate mesoderm cells could be induced from ADSCs and that they could differentiate well after cocultured with decellularized scaffolds.

Enhancement of cisplatin cytotoxicity by Retigeric acid B involves blocking DNA repair and activating DR5 in prostate cancer cells.

Retigeric acid B (RAB), a natural compound isolated from lichen, has been demonstrated to inhibit cell growth and promote apoptosis in prostate cancer (PCa) cells. The present study evaluated the function of RAB combined with clinical chemotherapeutic drugs in PCa cell lines by MTT assay, reverse transcription quantitative polymerase chain reaction and western blot analysis, and identified that RAB at low doses produced significant synergistic cytotoxicity in combination with cisplatin (CDDP); however, no marked synergism between RAB and the other chemotherapeutics was observed. Additional studies revealed that RAB exerted an inhibitory effect on DNA damage repair pathways, including the nucleotide excision repair and mismatch repair pathways, which are involved in the sensitivity to CDDP-based chemotherapy, as suggested by the significantly downregulated expression of certain associated repair proteins. Notably, Excision repair cross-complementing 1, a critical gene in the nucleotide excision repair pathway, exhibited the most significant decrease. When combined with CDDP, RAB-mediated impairment of DNA repair resulted in prolonged DNA damage, as demonstrated by the long-lasting appearance of phosphorylation of histone H2AX at Ser139, which potentially enhanced the chemosensitivity to CDDP. Concurrently, the proapoptotic protein death receptor 5 (DR5) was activated by RAB, which also enhanced the chemotherapeutic response of CDDP. Knockdown of DR5 partially blocked RAB-CDDP synergism, suggesting the crucial involvement of DR5 in this event. The results of the present study identified that RAB functioned synergistically with CDDP to increase the efficacy of CDDP by inhibiting DNA damage repair and activating DR5, suggesting the mechanistic basis for the antitumor effect of RAB in combination with current chemotherapeutics.

Anti-Cancer Effects of Paris Polyphylla Ethanol Extract by Inducing Cancer Cell Apoptosis and Cycle Arrest in Prostate Cancer Cells.

OBJECTIVE: To evaluate the potential anti-prostate cancer effects of Paris polyphylla ethanol extract (PPEE) and its underlying mechanisms. MATERIALS AND METHODS: The anti-proliferation activity of PPEE was tested on PC3 and DU145 cells using Cell Counting Kit-8 assay. The pro-apoptotic and cell cycle arrest effects of PPEE were confirmed by flow cytometry. Apoptosis of prostate cancer cells was induced by PPEE through endogenous and exogenous pathways. A mouse xenograft model was used to examine its anti-prostate cancer effects in vivo. RESULTS: We found that the IC50 of PPEE on PC3 cells was 3.98 µg/ml and the IC50 of PPEE on DU145 cells was 8 µg/ml. PPEE induced prostate cancer cell apoptosis in a concentration dependent manner, through endogenous and exogenous pathways. PPEE induced PC3 cell cycle arrest in G0/G1 and G2/M phases, while in DU145cell it induced cell arrest in the G0/G1 phase. PPEE inhibited the growth of prostate cancer cells in vivo. CONCLUSION: PPEE could inhibit prostate cancer growth in vitro and in vivo, induce apoptosis of prostate cancer cells, and cause cell cycle arrest, which laid the foundation for further research on the anti-tumor mechanism of PPEE.

Recellularization of well-preserved decellularized kidney scaffold using adipose tissue-derived stem cells.

To establish a recellularization kidney model by using adipose tissue-derived stem cells (ADSCs) as seeding cells and to investigate the growth and differentiation of ADSCs in decellularized kidney scaffolds. ADSCs were isolated using a modified method and then identified using flow cytometry analysis. Osteogenesis and adipogenesis differentiation were performed. Rat kidneys were decellularized using 0.5% sodium dodecyl sulfate. Immunofluorescence, immunohistochemistry, and scanning electron microscope were conducted to examine the scaffold microstructure. The decellularized kidney scaffold was seeded with ADSCs antegrade through the artery or retrograde through the ureter and cultured for 5-10 days. Hematoxylin and eosin staining, immunofluorescence, and immunohistochemistry were applied to assess growth and differentiation of seeding cells within the scaffold. ADSCs populated within the glomerular, vascular, and tubular area of kidney scaffolds. Cells differentiated toward endothelial or tubular cells. Stromal cell-derived factor 1 promoted cell attachment in the scaffold. These findings suggest that ADSCs can be used as an additional new source of seeding cells within decellularized kidney scaffold. This combination may offer an alternative to donor kidney transplant. In this way, autologous ADSCs can be utilized as seeding cells in cell-scaffold kidney regeneration for further clinical transplantation. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 805-814, 2018.

Paris Polyphylla-Derived Saponins Inhibit Growth of Bladder Cancer Cells by Inducing Mutant P53 Degradation While Up-Regulating CDKN1A Expression.

OBJECTIVES: Paris polyphylla var. yunnanensis (PPVY), a Chinese herb, has long been used for cancer treatment, and its steroidal saponins are suggested to exert an anti-tumor activity, however, the underlying mechanism is incompletely understood and their effect on bladder cancer (BC) remains unknown. The present study is thus designed to address these issues. MATERIAL AND METHODS: Total steroidal saponins were extracted with ethanol from PPVY and used to treat BC cells (HT1197 and J82 carrying mutant p53). Gene expression was determined using qPCR and immunoblotting and cell cycle analyzed using flow cytometry. DNA damage response activation was assessed using immunofluorescence staining. RESULTS: PPVY saponins treatment led to dose-dependent declines in the number of both HT1197 and J82 cells with IC50 approximately 1.2 µg/ml, which was coupled with strong growth arrest at G2/M phase and the activation of DNA damage response pathway. Moreover, the clonogenic potential of these cells was severely impaired even in the presence of low concentrations of PPVY saponins. Mechanistically, PPVY saponins induced the degradation of mutant p53 while stimulated CDKN1A gene transcription. Phosphorylated AKT was diminished in PPVY saponin-treated cells, but its specific inhibitor LY294002 exhibited significantly weaker efficacy in inducing CDKN1A expression than did PPVY saponins. CONCLUSION: PPVY saponins activate DNA damage response pathway, degrade mutant p53 and stimulate CDKN1A expression, thereby inhibiting BC cell growth. Given their poor absorption via oral administration, PPVY saponins may be applicable for intravesical instillations in BC treatment.

Construction of engineered corpus cavernosum with primary mesenchymal stem cells in vitro.

Various methods have been used to reconstruct the penis. The objective of this study was to investigate the feasibility of constructing engineered corpus cavernosum with primary mesenchymal stem cells (MSCs) in a rabbit model in vitro. Acellular corporal matrices (ACMs) were obtained from adult rabbit penile tissues through an established decellularization procedure. MSCs were separated, purified, and then seeded on ACMs to construct engineered corpus cavernosum. The seeded ACMs were subsequently cultured in an incubator for 14 days. Histological analyses showed that MSCs seeded on the ACMs had proliferated and were well distributed. Detection of CD31, vWF, smooth muscle actin (SMA), and myosin protein as well as vWF and myosin mRNA revealed that the MSCs had differentiated into endothelial cells and smooth muscle cells. In addition, cell morphology of the engineered corpus cavernosum was directly observed by transmission electron microscopy. This study demonstrated that engineered corpus cavernosum could be successfully constructed using primary MSCs in vitro. This technology represents another step towards developing engineered corpus cavernosum in vitro.

Ursolic Acid Induces Apoptosis of Prostate Cancer Cells via the PI3K/Akt/mTOR Pathway.

Ursolic acid (UA), a pentacyclic triterpenoid, is known to exert antitumor activity in breast, lung, liver and colon cancers. Nonetheless, the underlying mechanism of ursolic acid in prostate cancer cells still remains unclear. In the present study, we report the chemotherapeutic effects of ursolic acid as assessed using in vitro and in vivo models. Treatment of human prostate cancer cells (LNCaP and PC-3) with UA inhibited the proliferation and induced apoptosis in both cell lines as characterized by the increased Annexin V-binding. The induction of apoptosis by UA was associated with a decrease in the levels of Bcl-2, Bcl-xl, survivin, and activated caspase-3. Treatment with UA also inhibited the expression of phosphatidylinositol-3-kinase (PI3K), phosphorylation of Akt and mTOR signaling proteins. Further, administration of UA significantly inhibited the growth of LNCaP prostate tumor xenografts in athymic nude mice, which was associated with inhibition of cell proliferation, induction of apoptosis of tumor cells and decreased expression of PI3K downstream factors, such as p-Akt and p-mTOR in tumor xenograft tissues. Our study demonstrates that UA not only inhibits cell growth but also induces apoptosis through modulation of the PI3K/Akt/mTOR pathway in human prostate cancer cells. We suggest that UA may be a new chemotherapeutic candidate against prostate cancer.