A necroptosis gene signature predicts prostate cancer recurrence, and is linked to somatic mutation, therapeutic landscape, and immune infiltration.

OBJECTIVE: Necroptosis, a type of programmed necrotic cell death, has been implicated in cancer biology and therapeutics. Improved risk stratification is required for prostate carcinoma in individuals. In view of the importance of necroptosis, this work proposed a necroptosis-based genetic model for recurrence prediction, and clarified its characteristics. METHODS: A least absolute shrinkage and selection operator (LASSO) regression analysis was conducted based upon transcriptome data of necroptosis genes with clinical information in the Cancer Genome Atlas (TCGA) prostate carcinoma samples, which were externally verified in the GSE116918 cohort. Somatic mutation was characterized by Maftools method. The drug sensitivity was estimated via OncoPredict algorithm. T-cell inflammation score and tumor mutational burden (TMB) score were computed for inferring immunotherapy response. CIBERSORT was adopted for scoring the infiltration of immune cell compositions. RESULTS: The necroptosis gene model was defined, composed of BCL2, BCL2L11, BNIP3, CASP8, CYLD, HDAC9, IDH2, IPMK, MYC, PLK1, TNF, TNFRSF1A, and TSC1. Considering external verification, this model effectively predicted recurrence-free survival, notably within one year (area under the curve (AUC) = 0.841, 0.706, 0.776, and 0.893 in the discovery, verification, total and external independent sets, respectively). Patients who had a risk score > median value were defined as high risk, while those who had risk score ≤ median value were defined as low risk. Older age, more advanced T, N, M stage, shorter disease-free survival, and more recurred/progressed statuses were found in high-risk patients (all P<0.05). Moreover, the signature independently predicted patient recurrence (P<0.05). High-risk specimens had more frequent somatic mutation, especially of TP53, BSN, APC, TRANK1, DNAH9, and SALL1 (all P<0.05). The heterogeneity in sensitivity to small-molecule compounds was investigated in low- and high-risk patients. Also, high-risk individuals responded better to immunotherapy (P<0.05). CONCLUSION: Altogether, the necroptosis gene signature may effectively predict prostatic carcinoma recurrence and therapeutic responses, but its clinical feasibility must be verified.

Inflammasome Inhibition Prevents Motor Deficit and Cerebellar Degeneration Induced by Chronic Methamphetamine Administration.

Methamphetamine (METH), a psychostimulant, has the potential to cause neurodegeneration by targeting the cerebrum and cerebellum. It has been suggested that the NLRP3 inflammasome may be responsible for the neurotoxicity caused by METH. However, the role of NLRP3 in METH-induced cerebellar Purkinje cell (PC) degeneration and the underlying mechanism remain elusive. This study aims to determine the consequences of NLRP3 modulation and the underlying mechanism of chronic METH-induced cerebellar PC degeneration. In METH mice models, increased NLRP3 expression, PC degeneration, myelin sheath destruction, axon degeneration, glial cell activation, and motor coordination impairment were observed. Using the NLRP3 inhibitor MCC950, we found that inhibiting NLRP3 alleviated the above-mentioned motor deficits and cerebellar pathologies. Furthermore, decreased mature IL-1ß expression mediated by Caspase 1 in the cerebellum may be associated with the neuroprotective effects of NLRP3 inflammasome inhibition. Collectively, these findings suggest that mature IL-1ß secretion mediated by NLRP3-ASC-Caspase 1 may be a critical step in METH-induced cerebellar degeneration and highlight the neuroprotective properties of inflammasome inhibition in cerebellar degeneration.

Scalable Growth of Organic Single-Crystal Films via an Orientation Filter Funnel for High-Performance Transistors with Excellent Uniformity.

Organic single-crystal films (OSCFs) provide an unprecedented opportunity for the development of new-generation organic single-crystal electronics. However, crystallization of organic films is normally governed by stochastic nucleation and incoherent growth, posing a formidable challenge to grow large-sized OSCFs. Here, an "orientation filter funnel" concept is presented for the scalable growth of OSCFs with well-aligned, singly orientated crystals. By rationally designing solvent wetting/dewetting patterns on the substrate, this approach can produce seed crystals with the same crystallographic orientation and then maintain epitaxial growth of these crystals, enabling the formation of large-area OSCFs. As a result, this unique concept for crystal growth not only enhances the average mobility of organic film by 4.5-fold but also improves its uniformity of electrical properties, with a low mobility variable coefficient of 9.8%, the new lowest record among organic devices. The method offers a general and scalable route to produce OSCFs toward real-word electronic applications.

Triptolide inhibits JAK2/STAT3 signaling and induces lethal autophagy through ROS generation in cisplatin­resistant SKOV3/DDP ovarian cancer cells.

Advanced and recurrent ovarian cancer has a poor prognosis and is frequently resistant to numerous therapeutics; thus, safe and effective drugs are needed to combat this disease. Previous studies have demonstrated that triptolide (TPL) exhibits anticancer and sensitization effects against cisplatin (DDP)­resistant ovarian cancer both in vitro and in vivo by inducing apoptosis; however, the involvement of autophagy induced by TPL in resistant ovarian carcinoma remains unclear. In the present study, the results revealed that TPL induced autophagy to facilitate SKOV3/DDP ovarian cancer cell death. The xenograft experiment revealed that the autophagy inhibitor CQ significantly reduced TPL­mediated chemosensitization and tumor growth inhibition. Mechanically, TPL­induced autophagy in SKOV3/DDP cells was associated with the induction of ROS generation and inhibition of the Janus kinase 2 (JAK2)/signal transducer and activator of transcription­3 (STAT3) pathway. The inhibitory effect of TPL on the JAK2/STAT3 pathway could be restored in the presence of the antioxidant NAC. Furthermore, it was further determined that TPL disrupted the interaction between Mcl­1 and Beclin1, which was prevented by the JAK2/STAT3 signaling activator IL­6. Overall, the present results revealed a novel molecular mechanism whereby TPL induced lethal autophagy through the ROS­JAK2/STAT3 signaling cascade in SKOV3/DDP cells. The present study has provided the groundwork for future application of TPL in the treatment of ovarian cancer.

Fast deposition of an ultrathin, highly crystalline organic semiconductor film for high-performance transistors.

Ultrathin organic semiconductor (OSC) crystalline films hold the promise of achieving high-performance, flexible, and transparent organic electronic devices. However, fast and high-throughput solution deposition of uniform pinhole-free ultrathin OSC crystalline films over a large area remains a challenge. Here, we demonstrate that a mixed solvent system can obviously alter the fluid flow dynamics and significantly improve the blade-coating quality of the film, enabling us to achieve a large-area continuous and smooth bis(triethylsilylethynyl)anthradithiophene (Dif-TES-ADT) ultrathin film at a fast coating speed of ∼1 mm s-1, much superior to the 30-50 µm s-1 for conventional methods. Also, the ultrathin, highly crystalline Dif-TES-ADT film-based organic thin-film transistors (OTFTs) exhibit a maximum mobility up to 5.54 cm2 V-1 s-1, which is on par with the Dif-TES-ADT single crystal-based devices and among the highest for Dif-TES-ADT film-based devices. This finding should open a new route to achieve ultrathin OSC crystalline film-based high-performance flexible and transparent electronics.

Layer-Defining Strategy to Grow Two-Dimensional Molecular Crystals on a Liquid Surface down to the Monolayer Limit.

Two-dimensional molecular crystals (2DMCs) open a new door for the controllable growth of 2D materials by molecular design with a energy gap and solution processability. However, the growth of 2DMCs with defined molecular layers remains full of challenges. Herein, we report a novel method to produce various 2DMCs with a defined number of molecular layers. When the surface tension and viscosity are tuned to control the spreading of the solution on the liquid surface, large-area quasi-freestanding 2DMCs from bulk size down to the monolayer limit are obtained, which makes it possible to probe the intrinsic layer-dependent optoelectronic properties of organic semiconductors down to the physical limit, and paves the way for the application of 2DMCs in new optoelectronic devices and technologies.

Impact of Taurine on the proliferation and apoptosis of human cervical carcinoma cells and its mechanism.

BACKGROUND: Cervical cancer has the fourth highest incidence and mortality rate of all cancers in women worldwide; it seriously harms their physical and mental health. The aim of this study was to observe the roles and preliminary mechanism of Taurine (Tau)-induced apoptosis in cervical cancer cells. METHODS: Cells from the human cervical cancer cell line SiHa were transfected with the recombinant plasmid pEGFP-N1-MST1 (mammalian sterile 20-like kinase 1); then, the cell proliferation activity was analyzed by the MTT assay, cell apoptosis by flow cytometry, and the related protein levels by Western blotting. RESULTS: Tau inhibited the proliferation of SiHa cells and induced apoptosis in these cells (the apoptotic rate was 21.95% in the Tau 160 mmol/L group and 30% in the Tau 320 mmol/L group), upregulated the expression of the MST1 (control, 0.53; Tau 40-320 mmol/L groups, 0.84-1.45) and Bax (control, 0.45; Tau 40-320 mmol/L groups, 0.64-1.51) proteins (P < 0.01), and downregulated the expression of Bcl-2 (control, 1.28, Tau 40-320 mmol/L groups, 0.93-0.47) (P < 0.01). The overexpression of MST1 promoted the apoptosis of SiHa cells, enhanced the apoptosis-inductive effects of Tau (P < 0.01), upregulated the expression of the proapoptotic proteins p73, p53, PUMA (p53 upregulated modulator of apoptosis), and caspase-3, and promoted the phosphorylation of YAP (Yes-associated protein). CONCLUSIONS: Tau inhibited the proliferation and induced the apoptosis of cervical cancer SiHa cells. The MST1 protein plays an important role in the Tau-induced apoptosis of cervical cancer cells.

Roles of the MST1-JNK signaling pathway in apoptosis of colorectal cancer cells induced by Taurine.

The aim of this study was to observe the impact of the mammalian sterile 20-like kinase 1-c-Jun N-terminal kinase (MST1-JNK) signaling pathway on apoptosis in colorectal cancer (CRC) cells induced by Taurine (Tau). Caco-2 and SW620 cells transfected with p-enhanced green fluorescent protein (EGFP)-MST1 or short interfering RNA (siRNA)-MST1 were treated with Tau for 48 h. Apoptosis was detected by flow cytometry, and the levels of MST1 and JNK were detected by western blotting. Compared with the control group, 80 mM Tau could significantly induce apoptosis of CRC cells, and the apoptotic rate increased with increasing Tau concentration (P < 0.01). Meanwhile, the protein levels of MST1 and phosphorylated (p)-JNK in Caco-2 cells increased significantly (P < 0.01). The apoptotic rate of the p-EGFP-MST1 plasmid-transfected cancer cells was significantly higher than that of the control group (P < 0.05); however, the apoptotic rate of the p-EGFP-MST1+Tau group was increased further (P < 0.01). Silencing the MST1 gene could decrease the apoptotic rate of cancer cells, and Tau treatment could reverse this decrease. Blocking the JNK signaling pathway significantly reduced the Tau-induced apoptotic rate of CRC cells. Thus, the MST1-JNK pathway plays an important role in Tau-induced apoptosis of CRC cells.

Molecular characterization of cu/Zn SOD gene in Asian clam Corbicula fluminea and mRNA expression and enzymatic activity modulation induced by metals.

The copper/zinc superoxide dismutase (Cu/Zn SOD) could effectively eliminate reactive oxygen species (ROS). In this study, the cDNA sequence of Cu/Zn SOD from Corbicula fluminea (designated as CfCu/Zn SOD) was cloned by the rapid amplification of cDNA ends (RACE) approaches. The full-length cDNA of CfCu/Zn SOD was of 1288 bp, including a 465 bp ORF encoding a protein of 154 amino acids. Two SOD family signatures were identified in CfCu/Zn SOD amino acids sequence. Multiple sequence alignments indicated that CfCu/Zn SOD amino acid sequences exhibited high similarities to those of other species. The tissue distribution of the CfCu/Zn SOD of C. fluminea was detected by fluorescent real-time quantitative PCR. The mRNA expression levels in digestive gland and gill were significantly higher than those of other four tissues. In response to metal ions (Cd2+, Cu2+, and Pb2+) challenge, the expression and enzymatic activities of CfCu/Zn SOD in the gills were measured after exposure for 0, 6, 12, 24, 48, and 72 h. The results showed that the mRNA expression and enzymatic activities of CfCu/Zn SOD could be induced by three metal ions. After Cd2+ and Cu2+ exposure, the mRNA expression levels increased gradually and reach the peak at 24 h, afterwards it slowed down. The change trends of enzymatic activities were similar to the mRNA expression. After Pb2+ exposure, the expression and activities CfCu/Zn SOD were raised up gradually and reach the highest value at 72 h. All these results indicated that the mRNA expression and enzymatic activity of CfCu/Zn SOD are sensitive to Cd2+, Cu2+ and Pb2+ ions and can be used as molecular biomarkers of metal pollution in water.

Effect of taurine on cell proliferation and apoptosis human lung cancer A549 cells.

To investigate the effects of taurine on cell proliferation and apoptosis, the human lung cancer A549 cell line and xenograft tumors in nude mice were used. The effects of taurine on cell proliferation and apoptosis were observed at time points of 24, 48 and 72 h after treatment using an MTT assay to detect the survival rate, and flow cytometry to detect the apoptotic rate. Western blot analysis was performed to examine the levels of p53 upregulated modulator of apoptosis (PUMA), BCL2, apoptosis regulator (Bcl-2) and BCL2-associated X, apoptosis regulator (Bax) in A549 cells. The level of PUMA, Bax and Bcl-2 proteins in the mouse xenograft tumors treated with taurine and/or exogenous PUMA were assessed by immunohistochemistry, with taurine suppressing the proliferation of the human lung cancer A549 cell line in a concentration-dependent manner, and it significantly enhanced the apoptosis rate at all concentrations. Taurine induced the significant upregulation of PUMA and Bax, but led to downregulation of Bcl-2. In comparison to the control group, taurine treatment markedly reduced the volume and weight of A549-derived xenograft tumors in nude mice. Expression of PUMA and Bax were upregulated in the xenograft tumors following taurine treatment, whereas Bcl-2 was downregulated. In addition, the inhibitory effect of taurine and exogenous PUMA on tumor growth was significantly higher than that of a single treatment of taurine or exogenous PUMA. It can therefore be concluded that taurine can inhibit cell proliferation of the human lung cancer A549 cell line and the growth of the xenograft tumors, whereas PUMA serves an important role in taurine-induced growth suppression.

Boosting oxygen reduction activity of spinel CoFe2O4 by strong interaction with hierarchical nitrogen-doped carbon nanocages.

The unique hierarchical nitrogen-doped carbon nanocages (hNCNC) are used as a new support to homogeneously immobilize spinel CoFe2O4 nanoparticles by a facile solvothermal method. The so-constructed hierarchical CoFe2O4/hNCNC catalyst exhibits a high oxygen reduction activity with an onset potential of 0.966V and half-wave potential of 0.819V versus reversible hydrogen electrode, far superior to the corresponding 0.846 and 0.742V for its counterpart of CoFe2O4/hCNC with undoped hierarchical carbon nanocages (hCNC) as the support, which locates at the top level for spinel-based catalysts to date. Consequently, the CoFe2O4/hNCNC displays the superior performance to the CoFe2O4/hCNC, when used as the cathode catalysts in the home-made Al-air batteries. X-ray photoelectron spectroscopy characterizations reveal the more charge transfer from CoFe2O4 to hNCNC than to hCNC, indicating the stronger interaction between CoFe2O4 and hNCNC due to the nitrogen participation. The enhanced interaction and hierarchical morphology favor the high dispersion and modification of electronic states for the active species as well as the mass transport during the oxygen reduction process, which plays a significant role in boosting the electrocatalytic performances. In addition, we noticed the high sensitivity of O 1s spectrum to the particle size and chemical environment for spinel oxides, which is used as an indicator to understand the evolution of ORR activities for all the CoFe2O4-related contrast catalysts. Accordingly, the well-defined structure-performance relationship is demonstrated by the combination of experimental characterizations with theoretical calculations. This study provides a promising strategy to develop efficient, inexpensive and durable oxygen reduction electrocatalysts by tuning the interaction between spinel metal oxides and the carbon-based supports.

Effect of taurine on the proliferation and apoptosis of human hepatocellular carcinoma HepG2 cells.

The aim of the present study was to observe the effect and molecular mechanism of taurine (Tau) on the cell proliferation and apoptosis of human hepatocellular carcinoma (HHCC) HepG2 cells. HHCC HepG2 cells were used as target cells, and the cell survival rate was assessed using a multi-time-step method. The p53 upregulated modulator of apoptosis (PUMA) gene was transiently transfected by lipofection and subsequently silenced with specific small interfering (si)RNA. The cell apoptosis rate was detected by flow cytometry, and protein expression levels were analyzed with western blotting. Addition of 20-160 mM Tau was shown to have a significant inhibitory effect on cell proliferation, while promoting the induction of HHCC HepG2 cell apoptosis (P<0.05). Transfection of the PUMA gene significantly enhanced the ability of Tau to inhibit proliferation and induce apoptosis of HepG2 cells. In addition, transfection of the PUMA gene increased the protein expression of B-cell lymphoma-2-associated X and reduced the expression of B-cell lymphoma-2 (P<0.05). Silencing the PUMA gene with specific siRNA was demonstrated to significantly reduce the ability of Tau to inhibit proliferation and induce the apoptosis of HHCC HepG2 cells (P<0.01). Therefore, the PUMA gene was shown to have an important role in mechanism underlying the effect that Tau exerts on cell proliferation and apoptosis in HHCC HepG2 cells.

γ-Secretase inhibitor inhibits bladder cancer cell drug resistance and invasion by reducing epithelial-mesenchymal transition.

A previous study by our group demonstrated that the expression levels of Notch 1 and Jagged 1 in bladder cancer cells was significantly lower compared with those in normal bladder mucosa, while the expression levels of Notch 1 and Jagged 1 in invasive bladder cancer were higher compared with those in superficial bladder cancer. The present study investigated the effect of the Notch signaling pathway on the drug resistance and invasiveness of bladder cancer cells. It was demonstrated that complete inhibition of the Notch signaling pathway induced significant morphological changes and inhibited cell proliferation and migration (P<0.05). Reverse transcription quantitative polymerase chain reaction and western blot analyses revealed that the mRNA and protein expression levels of E-cadherin were upregulated (P<0.05) and the mRNA and protein expression levels of N-cadherin, vimentin and α-smooth muscle actin were downregulated (P<0.05). The present study concluded that complete inhibition of the Notch signaling pathway inhibited cell proliferation and invasion, and reduced drug resistance in bladder cancer cells, a phenomenon which may be associated with the inhibition of the epithelial-mesenchymal transition.

Solution combustion synthesis of calcium phosphate particles for controlled release of bovine serum albumin.

Four different phase compositions of calcium phosphate (CaP) particles were prepared via a solution combustion method. X-ray diffraction (XRD) and Rietveld analysis results revealed that the variations in the nominal Ca/P (molar) ratios were found to provide a favorable control in the different proportions of CaP materials. Bovine serum albumin (BSA) was used as a model protein to study the loading and release behavior. The release profile indicated that the BSA release rates depended on the phase compositions of the CaP particles, and showed an order of TCP-BSA>BCP-1-BSA>BCP-2-BSA>HA-BSA. The results suggested that the BSA protein release rate can be controlled by varying the phase compositions of CaP carriers. Moreover, the release process involved two stages: firstly surface diffusion via ion exchange and secondly intraparticle diffusion.

Exogenous p53 upregulated modulator of apoptosis (PUMA) decreases growth of lung cancer A549 cells.

PURPOSE: To investigate the influence of exogenous p53 upregulated modulator of apoptosis (PUMA) expression on cell proliferation and apoptosis in human non-small cell lung cancer A549 cells and transplanted tumor cell growth in nude mice. MATERIALS AND METHODS: A549 cells were divided into the following groups: control, non- carrier (NC), PUMA (transfected with pCEP4- (HA) 2-PUMA plasmid), DDP (10 µg/mL cisplatin treatment) and PUMA+DDP (transfected with pCEP4-(HA)2-PUMA plasmid and 10 µg/mL cisplatin treatment). The MTT method was used to detect the cell survival rate. Cell apoptosis rates were measured by flow cytometry, and PUMA, Bax and Bcl-2 protein expression levels were measured by Western blotting. RESULTS: Compared to the control group, the PUMA, DDP and PUMA+DDP groups all had significantly decreased A549 cell proliferation (p<0.01), with the largest reduction in the PUMA+DDP group. Conversely, the apoptosis rates of the three groups were significantly increased (P<0.01), and the PUMA and DDP treatments were synergistic. Moreover, Bax protein levels significantly increased (p<0.01), while Bcl-2 protein levels significantly decreased (p<0.01). Finally, both the volume and the weights of transplanted tumors were significantly reduced (p<0.01), and the inhibition ratio of the PUMA+DDP group was significantly higher than in the single DDP or PUMA groups. CONCLUSIONS: Exogenous PUMA effectively inhibited lung cancer A549 cell proliferation and transplanted tumor growth by increasing Bax protein levels and reducing Bcl-2 protein levels.

MiR-221-induced PUMA silencing mediates immune evasion of bladder cancer cells.

Immune evasion of cancer cells is mainly due to the impaired transduction of apoptotic signals from immune cells to cancer cells, as well as inhibition of subsequent apoptosis signal cascades within the cancer cells. Over the past few decades, the research has focused more on the impaired transduction of the apoptotic signal from immune cells to cancer cells, rather than inhibition of the intracellular signaling pathways. In this study, miR­221 inhibitor was transfected into bladder cancer cell lines 5637, J82 and T24 to repress the expression of miR­221. As a result, the repression of miR­221 on p53 upregulated modulator of apoptosis (PUMA) was abolished, resulting in increased expression of the pro-apoptotic Bax and reduced expression of the anti-apoptotic Bcl-2, which promotes apoptosis of bladder cancer cells. The expression of MMP-2, MMP-9 and VEGF-C were reduced, resulting in reduced invasiveness and infiltration capability of bladder cancer cells, thereby inhibiting the immune evasion of bladder cancer cells.

Taurine induces the apoptosis of breast cancer cells by regulating apoptosis-related proteins of mitochondria.

Taurine (Tau), the most abundant free amino acid in humans has numerous potential health benefits through its antioxidant and anti-inflammatory properties. However, limited studies have assessed its effect on tumors and the antitumor mechanism remains unknown. The present study investigated the cellular and molecular changes induced by Tau, leading to the induction of apoptosis in human breast cancer cell lines MCF-7 and MDA-MB-231. MCF-7 is p53 proficient (p53+/+) and MDA-MB-231 is a p53 null mutant (p53-/-). Cell proliferation and viability were assessed by MTT. Flow cytometry and hoechst33342 fluorescent staining were employed to detect apoptosis. Spectrophotometry was used to detect caspase-3 activity. Reverse transcription-polymerase chain reaction and western blot analysis were used to detect the levels of mRNA and proteins of p53-upregulated modulator of apoptosis (PUMA), Bax and Bcl-2. Finally, the affect of Tau on the growth of MDA-MB-231-cell-nude mice xenografts was examined. In the study, Tau inhibited growth and induced apoptosis of the two cell lines in a concentration- and time-dependent manner. Notably, the inhibitory effect of Tau on p53-/- cancer cells was clearly significant compared to the p53+/+ cancer cells. Further studies showed that Tau promoted apoptosis in human breast cancer cells and inhibited the growth of tumor in nude mice by inducing the expression of PUMA, which further up- and downregulated the expression of Bax and Bcl-2 protein, giving rise to increased activation of caspase-3. Collectively, these results indicate that Tau is a potent candidate for the chemotherapy of breast cancer through increasing the PUMA expression independent of p53 status.

Mechanism of taurine-induced apoptosis in human colon cancer cells.

Taurine (Tau) has been shown to possess cancer therapeutic effect through induction of apoptosis, while the underlying molecular mechanism of its anti-cancer effect is not well understood. PUMA (p53-upregulated modulator of apoptosis) plays an important role in the process of apoptosis induction in a variety of human tumor cells in both p53-dependent and -independent manners. However, whether PUMA is involved in the process of Tau-induced apoptosis in cancer cells has not been well studied. In the present study, we treated human colorectal cancer cells HT-29 (mutant p53) and LoVo (wild-type p53) with different concentrations of Tau, which led to the repression of cell proliferation and induction of apoptosis in both cell lines. Meanwhile, we also observed the increased expression of PUMA and high Bax/Bcl-2 ratios. To determine the role of PUMA in Tau-induced apoptosis, we used small interfering RNA interference to suppress PUMA expression. As a result, apoptosis was decreased in response to Tau treatment. All these results indicated that PUMA plays a critical role in Tau-induced apoptosis pathway in human colorectal cancer cells. Demonstration of the molecular mechanism involved in the anti-tumor effect of Tau may be useful in the therapeutic target selection for p53-deficient colorectal cancer.

Effect of diallyl trisulfide on human ovarian cancer SKOV- 3/DDP cell apoptosis.

AIM: To investigate the effects of diallyl trisulfide (DT) on apoptosis of cisplatin (DDP)-resistant human epithelial ovarian cancer SKOV-3 cells (SKOV-3/DDP), and the role of p53 upregulated modulator of apoptosis (PUMA). METHODS: SKOV-3/DDP cells were randomly divided into control, DT, DPP and DPP+DT groups, which were treated with DT or combined DT and DDP. All cells were incubated for 48 h. and apoptosis rates were assessed by flow cytometry. mRNA and protein expression of PUMA, Bax and Bcl-2 was determined by RT-PCR and Western blot assays, respectively. RESULTS: Compared with control group, the apoptosis rates of SKOV-3/DDP cells in DT groups were obviously increased, with dose-dependence (P < 0.05), the mRNA and protein expressions of PUMA, Bax also being up-regulated (P < 0.05), while those of Bcl-2 were down-regulated (P < 0.05). Compared with DT groups, the apoptosis rate in the DDP+DT group was significantly increased (P < 0.05). After knockdown of PUMA with specific siRNA, the apoptosis rate of SKOV-3/DDP cells was obviously decreased (P < 0.05). CONCLUSION: DT can promote the apoptosis of SKOV-3/DDP cells with PUMA playing a critical role.