Antioxidant, AChE inhibitory, and anticancer effects of Verbascum thapsus extract.

Verbascum thapsus (VT) is a medicinal plant that is used in folk medicine to treat a variety of ailments. For this study, the biological functions of VT methanol extract were determined in vitro. The plant's methanol extract was created through the maceration process. The phytochemical composition of plant extracts was investigated using liquid chromatography-electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS). The antioxidant capacity of the extract was determined using the DPPH (2,2-diphenyl-1-picrylhydrazil) and ABTS (2,2-azinobis (3-ethylbenzothiazoline-6-sulfonic acid) tests and its cytotoxicity was assessed using the MTT ((3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, a tetrazole)) assay on the Caco-2 (human colorectal adenocarcinoma cells), LNCaP (Lymph Node Carcinoma of the Prostate), and HEK293 cell lines (Human embryonic kidney 293 cells) used to model colon, prostate, and non-cancerous cells. VT extract showed low DPPH and ABTS radical scavenging activities compared to standard antioxidants at 30 mg/ml concentration. In addition, it was determined that VT extract inhibited acetylcholinesterase enzyme.

A novel diagnostic method for distinguishing between Fe(IV) and •OH by using atrazine as a probe: Clarifying the nature of reactive intermediates formed by nitrilotriacetic acid assisted Fenton-like reaction.

In this work, we found that the distribution of two specific atrazine (ATZ) oxidation products (desethyl-atrazine (DEA) and desisopropyl-atrazine (DIA)) was different in oxidation processes involving aqueous ferryl ion (Fe(IV)) species and •OH. Specifically, the molar ratio of produced DEA to DIA (i.e., [DEA]/[DIA]) increased from 7.5 to 13 with increasing pH from 3 to 6 when ATZ was oxidized by Fe(IV), while the treatment of ATZ by •OH led to the [DEA]/[DIA] value of 2 which was independent of pH. Moreover, ATZ showed high reactivity towards Fe(IV) over a wide pH range, especially at near-neutral pH, at which ATZ oxidation in Fe(II)/peroxydisulfate system was even much faster than another well-defined Fe(IV) scavenger, the sulfoxides. By using this approach, it was obtained that the [DEA]/[DIA] value remained at 2 during ATZ transformation by the nitrilotriacetic acid (NTA) assisted Fenton-like (Fe(III)/H2O2) system, which was independent of solution pH and reactants dosage. This result clarified that •OH was the primary reactive intermediate formed in the NTA assisted Fe(III)/H2O2 system. This study not only developed a novel sensitive diagnostic tool for distinguishing Fe(IV) from •OH, but also provided more credible evidence to the nature of reactive intermediate in a commonly controversial system.

Assessment and mechanisms of microalgae growth inhibition by phosphonates: Effects of intrinsic toxicity and complexation.

The effects of phosphonates, the heavily-used antiscalants in reverse osmosis systems, on microalgae are controversial, although they are harmless to most aquatic organisms. Herein, we assessed the inhibitory effects of etidronic acid (HEDP) and diethylenetriamine penta(methylene phosphonic acid) (DTPMP) on algal growth and revealed the mechanisms involved in both intrinsic toxicity and complexation. The phosphonates showed weak influences on Scenedesmus sp. LX1 in the first 4 d of cultivation. In contrast, a significant growth inhibition was observed subsequently with half maximal effective concentrations of 57.6 and 35.7 mg/L for HEDP and DTPMP, respectively, at 10 d. The phosphonates had little effect on cellular energy transfer and oxidative stress, quantified by adenosine triphosphate level and superoxide dismutase activity, respectively, demonstrating weak intrinsic toxicities to algal cells. Phosphonates blocked the algal assimilation of iron ions through complexation. Severe iron deficiency limited photosynthetic activity and caused chlorophyll decline, resulting in a functional loss of the photosystem followed by complete algal growth inhibition at the late cultivation stage. Our findings point to a potential ecological impact wherein harmful algal blooms are induced by the natural degradation of phosphonates due to the release of both iron and phosphate ions that stimulate algal regrowth after disinhibition.

Recent Advances in Hemostasis at the Nanoscale.

Rapid and effective hemostatic materials have received wide attention not only in the battlefield but also in hospitals and clinics. Traditional hemostasis relies on materials with little designability which has many limitations. Nanohemostasis has been proposed since the use of peptides in hemostasis. Nanomaterials exhibit excellent adhesion, versatility, and designability compared to traditional materials, laying a good foundation for future hemostatic materials. This review first summarizes current hemostatic methods and materials, and then introduces several cutting-edge designs and applications of nanohemostatic materials such as polypeptide assembly, electrospinning of cyanoacrylate, and nanochitosan. Particularly, their advantages and working mechanisms are introduced. Finally, the challenges and prospects of nanohemostasis are discussed.

Novel role of SF1 in alleviating thyroid-associated ophthalmopathy through the AMPK/mTOR signaling pathway.

BACKGROUND/AIM: Thyroid-associated ophthalmopathy (TAO) is a chronic autoimmune disorder characterized by an increased volume of adipose/connective tissue. This study aims to explore whether steroidogenic factor 1 (SF1) is implicated in development of TAO through the adenosine monophosphate-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR) signaling pathway. METHODS: Initially, we extracted orbital preadipocytes from 10 TAO patients for culture and identification. After differentiation, cells were inoculated with plasmids with overexpressed SF1, and plasmids with siRNA against SF1, respectively. Then fat content and PGE2 secretion were measured by using ELISA. The levels of SF1, Bax, Bcl-2, Caspase3, Pref-1, PPARγ, Leptin, Adiponectin, p-AMPKαThr172, p-mTORSer2448, and p-S6KThr389 were detected by RT-qPCR and western blot analysis. Cell proliferation and apoptosis were measured by EdU and flow cytometry. RESULTS: TAO patients showed reduced SF1 expression in orbital preadipocytes. Overexpression of SF1 led to inhibited expression of Bcl-2, PPARγ, Leptin, Adiponectin and p-AMPKαThr172, fat content, cell proliferation and differentiation, but increased levels of Bax, Caspase3, Pref-1, p-mTORSer2448 and p-S6KThr389, PGE2 secretion and apoptosis rate. CONCLUSION: Our result showed up-regulated SF1 may relieve TAO through suppressing cell proliferation and differentiation, but accelerating cell apoptosis by inhibiting the activation of the AMPK/mTOR signaling pathway.

Interaction between 1,2-benzisothiazol-3(2H)-one and microalgae: Growth inhibition and detoxification mechanism.

Isothiazolinones, such as 1,2-benzisothiazol-3(2H)-one (BIT), are widely used as biocides for bacterial growth control in many domestic and industrial processes. Despite their advantages as biocides, they are highly toxic and pose a potential risk to the environment. This study investigated the inhibition process and detoxification mechanism involved in microalgal survival and growth recovery after BIT poisoning. BIT could seriously inhibit the growth of Scenedesmus sp. LX1, Chlorella sp. HQ, and Chlamydomonas reinhardtii with half maximal effective concentrations at 72 h (72h-EC50) of 1.70, 0.41, and 1.16 mg/L, respectively. The primary inhibition mechanism was the BIT-induced damage to microalgal photosynthetic systems. However, the inhibited strains could recover when their growth was not completely inhibited. The influence of this inhibiting effect on subsequent algal regrowth was negligible or weak. BIT consumption was the primary reason for their recovery. Notably, algae did not die even if their growth was completely inhibited. If the BIT concentration did not exceed a certain high level, then the inhibited algae could recover their growth relatively well. Microalgal generation of reduced glutathione (GSH) and the oxygen radical scavenging enzymes, superoxide dismutase (SOD) and catalase (CAT), played a key role in detoxification against BIT poisoning.

Primary squamous cell carcinoma of the pancreas with effective comprehensive treatment: A case report and literature review.

RATIONALE: Primary squamous cell carcinoma (SCC) of the pancreas is a rare entity since the pancreas lacks squamous cells. This condition is associated with a poor prognosis, and there is currently no optimal treatment strategy for it. PATIENT CONCERNS: A 64-year-old female patient with a complaint of epigastric pain for 3 months was referred to our hospital. DIAGNOSES: She was finally diagnosed with primary SCC of the pancreas with lymph node metastasis on the basis of radiological and pathological findings. INTERVENTIONS: She received chemoradiation along with targeted therapy and was provided with treatment response evaluation through PET/CT. OUTCOMES: She eventually died of tumor progression after 8 months. LESSONS: Primary SCC of the pancreas is associated with a poor prognosis. Comprehensive therapy and proper radiologic evaluation may facilitate prolonged survival of these patients.

Electric Field-Assisted In Situ Precise Deposition of Electrospun γ-Fe2O3/Polyurethane Nanofibers for Magnetic Hyperthermia.

A facial electrospinning method of in situ precise fabricating magnetic fibrous membrane composed of polyurethane (PU) nanofibers decorated with superparamagnetic γ-Fe2O3 nanoparticles with simultaneous heat generation in response to alternating magnetic field (AMF) is reported. In this method, a conical aluminum auxiliary electrode is used to regulate the electrostatic field and affect the process of electrospinning for the in situ rapid and precise deposition of electrospun γ-Fe2O3/PU fibers. The auxiliary conical electrode can extend the jet stabilization zone of the precursor solution four times longer than that of without auxiliary electrode, which can achieve the precise control of the fiber deposition area. Moreover, the electrospun composite fibrous membranes show a rapid temperature increase from room temperature to 43 °C in 70 s under the AMF, which exhibits faster heating rate and higher heating temperature compared to the samples fabricated without the assist of the auxiliary electrode. The present results demonstrate that the in situ precise electrospinning with the help of an auxiliary conical electrode has the potential as a manipulative method for preparing magnetic composite fibers as well as magnetic hyperthermia of cancer therapy.

Tolerance and resistance characteristics of microalgae Scenedesmus sp. LX1 to methylisothiazolinone.

Methylisothiazolinone (MIT) has been widely used to control bacterial growth in reverse osmosis (RO) systems. However, MIT's toxicity on microalgae should be determined because residual MIT is concentrated into RO concentrate (ROC) and might have a severe impact on microalgae-based ROC treatment. This study investigated the tolerance of Scenedesmus sp. LX1 to MIT and revealed the mechanism of algal growth inhibition and toxicity resistance. Scenedesmus sp. LX1 was inhibited by MIT with a half-maximal effective concentration at 72 h (72 h-EC50) of 1.00 mg/L, but the strain recovered from the inhibition when its growth was not completely inhibited. It was observed that this inhibition's effect on subsequent growth was weak, and the removal of MIT was the primary reason for the recovery. Properly increasing the initial algal density significantly shortened the adaptation time for accelerated recovery in a MIT-containing culture. Photosynthesis damage by MIT was one of the primary reasons for growth inhibition, but microalgal cell respiration and adenosine triphosphate (ATP) synthesis were not completely inhibited, and the algae were still alive even when growth was completely inhibited, which was notably different from observations made with bacteria and fungi. The algae synthesized more chlorophyll, antioxidant enzymes of superoxide dismutase (SOD) and catalase (CAT), and small molecules, such as reduced glutathione (GSH), to resist MIT poisoning. The microalgae-based process could treat the MIT-containing ROC, since MIT was added for only several hours a week in municipal wastewater reclamation RO processes, and the MIT average concentration was considerably lower than the maximum concentration that algae could tolerate.

Facile Fabrication of Multi-hierarchical Porous Polyaniline Composite as Pressure Sensor and Gas Sensor with Adjustable Sensitivity.

A multi-hierarchical porous polyaniline (PANI) composite which could be used in good performance pressure sensor and adjustable sensitivity gas sensor has been fabricated by a facile in situ polymerization. Commercial grade sponge was utilized as a template scaffold to deposit PANI via in situ polymerization. With abundant interconnected pores throughout the whole structure, the sponge provided sufficient surface for the growth of PANI nanobranches. The flexible porous structure helped the composite to show high performance in pressure detection with fast response and favorable recoverability and gas detection with adjustable sensitivity. The sensing mechanism of the PANI/sponge-based flexible sensor has also been discussed. The results indicate that this work provides a feasible approach to fabricate efficient sensors with advantages of low cost, facile preparation, and easy signal collection.

A Normalization-Free and Nonparametric Method Sharpens Large-Scale Transcriptome Analysis and Reveals Common Gene Alteration Patterns in Cancers.

Heterogeneity in transcriptional data hampers the identification of differentially expressed genes (DEGs) and understanding of cancer, essentially because current methods rely on cross-sample normalization and/or distribution assumption-both sensitive to heterogeneous values. Here, we developed a new method, Cross-Value Association Analysis (CVAA), which overcomes the limitation and is more robust to heterogeneous data than the other methods. Applying CVAA to a more complex pan-cancer dataset containing 5,540 transcriptomes discovered numerous new DEGs and many previously rarely explored pathways/processes; some of them were validated, both in vitro and in vivo, to be crucial in tumorigenesis, e.g., alcohol metabolism (ADH1B), chromosome remodeling (NCAPH) and complement system (Adipsin). Together, we present a sharper tool to navigate large-scale expression data and gain new mechanistic insights into tumorigenesis.

Chitosan nanostructures by in situ electrospinning for high-efficiency PM2.5 capture.

Nanofiber-based air filters and electrostatic precipitation have stimulated considerable interest because of their high-efficiency for PM2.5 capture. In this paper, we introduce a new method of in situ electrospinning (e-spinning) of nanostructures into a polluted enclosed space to efficiently clean the air. From the comparisons of different polymer precursors and different PM2.5 capture techniques, it can be seen that in situ e-spinning of chitosan aqueous solution into the air exhibits the best PM2.5 capture efficiency, which may be attributed to the stronger polarity of chitosan and the synergistic effect of the strong electrostatic adsorption and surface adhesion of the electrospun (e-spun) nanofibers. A removal rate as high as 3.7 µg m-3 s-1 was obtained using this technology with a high efficiency of more than 95% PM2.5 capture. The results obtained from a field test in a smoking room (∼5 × 6 × 3 m3) are still in great agreement with those obtained in an experimental box (∼25 × 30 × 35 cm3). More importantly, chitosan is non-toxic and biodegradable, and is harmless to human health when used as a precursor for in situ e-spinning for PM2.5 capture.

Large-scale DNA methylation expression analysis across 12 solid cancers reveals hypermethylation in the calcium-signaling pathway.

Tumorigenesis is linked to the role of DNA methylation in gene expression regulation. Yet, cancer is a highly heterogeneous disease in which the global pattern of DNA methylation and gene expression, especially across diverse cancers, is not well understood. We investigated DNA methylation status and its association with gene expressions across 12 solid cancer types obtained from The Cancer Genome Atlas. Results showed that global hypermethylation was an important characteristic across all 12 cancer types. Moreover, there were more epigenetically silenced than epigenetically activated genes across the cancers. Further analysis identified epigenetically silenced genes shared in the calcium-signaling pathway across the different cancer types. Reversing the aberrant DNA methylation of genes involved in the calcium-signaling pathway could be an effective strategy for suppressing cancers and developing anti-cancer drugs.

Calotropin from Asclepias curasavica induces cell cycle arrest and apoptosis in cisplatin-resistant lung cancer cells.

Calotropin (M11), an active compound isolated from Asclepias curasavica L., was found to exert strong inhibitory and pro-apoptotic activity specifically against cisplatin-induced resistant non-small cell lung cancer (NSCLC) cells (A549/CDDP). Molecular mechanism study revealed that M11 induced cell cycle arrest at the G2/M phase through down-regulating cyclins, CDK1, CDK2 and up-regulating p53 and p21. Furthermore, M11 accelerated apoptosis through the mitochondrial apoptotic pathway which was accompanied by increase Bax/Bcl-2 ratio, decrease in mitochondrial membrane potential, increase in reactive oxygen species production, activations of caspases 3 and 9 as well as cleavage of poly ADP-ribose polymerase (PARP). The activation and phosphorylation of JNK was also found to be involved in M11-induced apoptosis, and SP610025 (specific JNK inhibitor) partially prevented apoptosis induced by M11. In contrast, all of the effects that M11 induce cell cycle arrest and apoptosis in A549/CDDP cells were not significant in A549 cells. Drugs with higher sensitivity against resistant tumor cells than the parent cells are rather rare. Results of this study supported the potential application of M11 on the non-small lung cancer (NSCLC) with cisplatin resistance.

TGF-ß and EGF induced HLA-I downregulation is associated with epithelial-mesenchymal transition (EMT) through upregulation of snail in prostate cancer cells.

Human leukocyte antigen class I antigens (HLA-I) is essential in immune response by presenting antigenic peptides to cytotoxic T lymphocytes. Downregulation of HLA-I is observed in primary and metastatic prostate cancers, which facilitates them escape from immune surveillance, thereby promotes prostate cancer progression. In addition, elevated level of growth factors like TGF-ß or EGF in microenvironment is related to the prostate cancer deterioration. Thus, we wondered whether TGF-ß or EGF was involved in the regulation of HLA-I during the development of prostate cancer cells. In this study, we demonstrated that TGF-ß and EGF both downregulated the expression of HLA-I, thereby attenuated the cytotoxic T cell mediated lysis of prostate cancer cells. Next, we revealed that TGF-ß and EGF induced downregulation of HLA-I is associated with classical epithelial-mesenchymal transition (EMT) morphological changes and expression profiles. We further illustrated that overexpression of Snail is crucial for HLA-I downregulation and its association with EMT. At last, we discussed that NF-κB/p65 is the plausible target for Snail to induce HLA-I downregulation. Taken together, this is the first evidence to reveal that both TGF-ß and EGF can induce HLA-I downregulation which is then proven to be associated with EMT in prostate cancer cells. These discoveries provide a deeper understanding of growth factors induced immune escape and introduce potential therapeutic targets for prostate cancers.

Transdifferentiation of human adipose-derived stem cells into urothelial cells: potential for urinary tract tissue engineering.

Autologous urothelial cells (UCs) provide a cell source for urinary tissue engineering because they can be used safely due to their lack of immunogenicity. However, these cells cannot be harvested under the following circumstances: malignancy, infection and organ loss, etc. Human adipose-derived stem cells (HADSCs) possess the traits of high differentiation potential and ease of isolation, representing a promising resource for tissue engineering and regenerative medicine. Nevertheless, HADSCs have been poorly investigated in urology and the optimal approaches to induce HADSCs into urothelium are still under investigation. In this study, we hypothesized that the change of microenvironment by a conditioned medium was essential for the transdifferentiation of HADSCs into UCs. We then used a conditioned medium derived from urothelium to alternate the microenvironment of HADSCs. After 14 days of culture in a conditioned medium, about 25-50% HADSCs changed their morphology into polygonal epithelium-like shapes. In addition, these cells expressed up-regulating of urothelial lineage-specific markers (uroplakin 2and cytokeratin-18) and down-regulating of mesenchymal marker (vimentin) in RNA and protein level, respectively, which confirmed that HADSCs were induced into urothelial lineage cells. We also measured the growth factors in the conditioned medium in order to analyze the molecular mechanisms regulating transdifferentiation. We observed that the expression levels of PDGF-BB and VEGF were significantly higher than those of the control group after 14 days induction, suggesting they were abundantly secreted into the medium during the culturing period. In conclusion, HADSCs showed in vitro the upregulation of markers for differentiation towards urothelial cells by culturing in an urothelial-conditioned medium, which provides an alternative cell source for potential use in urinary tract tissue engineering.

A surface-modified biodegradable urethral scaffold seeded with urethral epithelial cells.

BACKGROUND: Efficient cell adhesion and proliferation is a central issue in cell-based tissue engineering, which offers great promise for repair of urethral defects or strictures. This study evaluated the adhesion and growth of rabbit uroepithelium on a surface-modified three-dimensional poly-L-lactic acid (PLLA) scaffold. METHODS: Urethral mucosa were harvested from male New Zealand rabbits and the urothelium were dissociated and then cultured. Immunocytochemistry on cultured uroepithelium for pancytokeratin and uroplakin II and TE-7 confirmed pure populations. After in vitro proliferation, cells were seeded onto a surface-modified urethral scaffold with non-knitted filaments. The morphology and viability of the cells were examined by immunohistochemical and fluorescence staining. Inverted and scanning microscopes were used to document cell growth and adhesion. RESULTS: Three to five days after primary culture, the uroepithelial cells gradually became confluent, assuming a cobblestone pattern. The filaments of the urethral scaffold had excellent biocompatibility and allowed growth of the uroepithelium, without affecting viability. The uroepithelial cells adhered to and grew well on the scaffold. After 3 - 7 days, the cells grew vigorously and meshes of the scaffold were full of uroepitheliums. CONCLUSIONS: The surface-modified urethral scaffold with non-knitted filaments allows the growth of uroepithelium and can serve as a carrier for the tissue engineering of urethra.

Silencing PinX1 compromises telomere length maintenance as well as tumorigenicity in telomerase-positive human cancer cells.

The nucleolar protein PinX1 has been proposed to be a putative tumor suppressor due to its binding to and inhibition of the catalytic activity of telomerase, an enzyme that is highly expressed in most human cancers in which it counteracts telomere shortening-induced senescence to confer cancer cell immortalization. However, the role of PinX1 in telomere regulation, as well as in cancer, is still poorly understood. In this study, we showed that the PinX1 protein is constitutively expressed in various human cells regardless of their telomerase activity and malignant status. Most interestingly, we found that silencing PinX1 expression by a potent short hairpin RNA construct led to a robust telomere length shortening and growth inhibition in telomerase-positive but not in telomerase-negative human cancer cells. We further showed that silencing PinX1 significantly reduced the endogenous association of telomerase with the Pot1-containing telomeric protein complex, and therefore, could account for the phenotypic telomere shortening in the affected telomerase-positive cancer cells. Our results thus reveal a novel positive role for PinX1 in telomerase/telomere regulations and suggest that the constitutive expression of PinX1 attributes to telomere maintenance by telomerase and tumorigenicity in cancer cells.

Vaporesection for managing benign prostatic hyperplasia using a 2-microm continuous-wave laser: a prospective trial with 1-year follow-up.

OBJECTIVE: To explore the safety and clinical efficacy of continuous-wave laser vaporesection for the treatment of obstructive benign prostatic hyperplasia (BPH). PATIENTS AND METHODS: We treated 72 consecutive patients with obstructive BPH using a 70 W 2-microm continuous-wave laser. The mean (range) age of the patients was 68.6 (52-86) years. Before laser treatment, the patients were examined. The mean (SD, range) prostatic volume was 65.8 (21.7, 36-108) mL. The operative outcomes assessed were: resection time, transfusion rate, catheter time, and haemoglobin and serum sodium levels. The following variables were assessed before and after vaporesection: maximum urinary flow rate (Qmax), postvoiding residual urine volume (PVR), International Prostate Symptom Score (IPSS), Quality of Life Index (QoL) and sexual function. RESULTS: All cases were successful using general (two cases), epidural (28) or sacral block regional anaesthesia (42). The mean (SD) vaporesection time was 56 (12.8) min. None of the patients required a transfusion. The mean (SD) catheter time was 1.7 (0.6) days. The mean Qmax increased from 5.7 (1.2) mL/s before to 20.8 (2.1) mL/s after vaporesection and the PVR decreased from 150 to 36 mL. The IPSS and QoL scores improved after vaporesection from 24.6 (4.5) to 6.8 (1.2) and 4.8 (0.2) to 1.4 (0.3), respectively (P < 0.05). Apart from transient dysuria (8%) and irritative symptoms (29%), all patients were satisfied with voiding outcome after vaporesection and none had incontinence. CONCLUSION: Vaporesection using the 2-microm continuous-wave laser for the treatment of obstructive BPH is a safe and effective ablative procedure with minimal morbidity and rare bleeding.

[DNA damage induces BRCA1 distribution alteration in prostate cancer cell lines].

OBJECTIVE: To investigate the role of the tumor suppressor gene BRCA1 in response to DNA damage and to confirm that the function of the BRCA1 protein is regulated by a variety of mechanisms including transcriptional control, phosphorylation and protein-protein interaction. METHODS: With the human breast cell line MCF7 as the positive control, we determined the subcellular distribution of BRCA1 in the prostate cancer cell lines LNCaP, DU145 and PC3 by immunohistochemical staining and Western blotting analyses. RESULTS: BRCA1 was present in the prostate cancer cell lines LNCaP, DU145 and PC3. Ionizing radiation induced BRCA1 nuclear export, increasing from 14% to 40% in the cytoplasma (P < 0.01) and decreasing from 46% to 21% in the nuclei (P < 0.01). This DNA damage-induced BRCA1 nuclear export occurred only in the p53 wild-type but not in the p53 mutant cell line. The apoptosis rate of LNCaP cells was as high as 40% after nuclear export, with an obvious increase of cleaved caspase-3, which was correlated with BRCA1 nuclear-cytoplasmic shuttling. CONCLUSION: Cytoplasmic relocalization of the BRCA1 protein may be a mechanism whereby the BRCA1 function is regulated in response to DNA damage. Its induction of a higher rate of cell apoptosis indicates BRCA1 to be another good biomarker for the treatment of prostate cancer.