Astragaloside VI and cycloastragenol-6-O-beta-D-glucoside promote wound healing in vitro and in vivo.

BACKGROUND: Astragalus genus includes most of the common, historical herbal medicines that have various applications in Asian countries. However, clinical data and mechanistic insights into their actions are still lacking. PURPOSE: In this study, we aimed to examine the effects of astragalosides on wound healing in vitro and in vivo, as well as the underlying mechanisms of these actions. METHODS: The wound healing activity of astragalosides was investigated in human HaCaT keratinocytes, human dermal fibroblast (HDF) cells, and murine models of wound healing. RESULTS: All eight astragalosides studied enhanced epidermal growth factor receptor (EGFR) activity in HaCaT cells. Among them, astragaloside VI (AS-VI) showed the strongest EGFR activation. Consistently, AS-VI and cycloastragenol-6-O-beta-D-glucoside (CMG), which is the major metabolite of astragalosides, enhanced extracellular signal-regulated kinase (ERK) activity in a concentration-dependent manner. In agreement, both compounds induced EGFR-dependent cell proliferation and migration in HaCaT and HDF cells. In addition, we showed that AS-VI and CMG accelerated the healing of both sterile and infected wounds in vivo. These effects were associated with increased angiogenesis in the scar tissue. CONCLUSION: AS-VI and CMG increased the proliferation and migration of skin cells via activation of the EGFR/ERK signalling pathway, resulting in the improvement of wound healing in vitro and in vivo. These findings indicate the therapeutic potential of AS-VI and CMG to accelerate wound healing; additionally, they suggest the mechanistic basis of this activity.

Danshen extract circumvents drug resistance and represses cell growth in human oral cancer cells.

BACKGROUND: Danshen is a common traditional Chinese medicine used to treat neoplastic and chronic inflammatory diseases in China. However, the effects of Danshen on human oral cancer cells remain relatively unknown. This study investigated the antiproliferative effects of a Danshen extract on human oral cancer SAS, SCC25, OEC-M1, and KB drug-resistant cell lines and elucidated the possible underlying mechanism. METHODS: We investigated the anticancer potential of the Danshen extract in human oral cancer cell lines and an in vivo oral cancer xenograft mouse model. The expression of apoptosis-related molecules was evaluated through Western blotting, and the concentration of in vivo apoptotic markers was measured using immunohistochemical staining. The antitumor effects of 5-fluorouracil and the Danshen extract were compared. RESULTS: Cell proliferation assays revealed that the Danshen extract strongly inhibited oral cancer cell proliferation. Cell morphology studies revealed that the Danshen extract inhibited the growth of SAS, SCC25, and OEC-M1 cells by inducing apoptosis. The Flow cytometric analysis indicated that the Danshen extract induced cell cycle G0/G1 arrest. Immunoblotting analysis for the expression of active caspase-3 and X-linked inhibitor of apoptosis protein indicated that Danshen extract-induced apoptosis in human oral cancer SAS cells was mediated through the caspase pathway. Moreover, the Danshen extract significantly inhibited growth in the SAS xenograft mouse model. Furthermore, the Danshen extract circumvented drug resistance in KB drug-resistant oral cancer cells. CONCLUSION: The study results suggest that the Danshen extract could be a potential anticancer agent in oral cancer treatment.

Astragaloside II promotes intestinal epithelial repair by enhancing L-arginine uptake and activating the mTOR pathway.

Astragaloside II (AS II) extracted from Astragalus membranaceus has been reported to promote tissue wound repair. However, the effect of AS II on inflammatory bowel disease is unknown. We investigated the effects and mechanism of AS II on intestinal wound healing in both in vitro and in vivo models. Human intestinal Caco-2 cells were treated with multiple concentrations of AS II to assess cell proliferation, scratch wound closure, L-arginine uptake, cationic amino acid transporter activity, and activation of the mTOR signaling pathway. These effects were also measured in a mouse model of colitis. AS II promoted wound closure and increased cell proliferation, L-arginine uptake, CAT1 and CAT2 protein levels, total protein synthesis, and phosphorylation of mTOR, S6K, and 4E-BP1 in Caco-2 cells. These effects were suppressed by lysine or rapamycin treatment, suggesting that the enhanced arginine uptake mediates AS II-induced wound healing. Similar results were also observed in vivo. Our findings indicate that AS II can contribute to epithelial barrier repair following intestinal injury, and may offer a therapeutic avenue in treating irritable bowel disease.

Antiangiogenic activity of phthalides-enriched Angelica Sinensis extract by suppressing WSB-1/pVHL/HIF-1α/VEGF signaling in bladder cancer.

The hypoxia-inducible factor-1α (HIF-1α) plays a critical role in tumor angiogenesis. It has been reported that the acetone extract of Angelica sinensis (AE-AS) rich in phthalides is able to inhibit cancer cell proliferation. However, whether AE-AS reduces cancer angiogenesis remains unknown. In this study, we demonstrated that AE-AS significantly inhibited the angiogenesis in vitro and in vivo evidenced by attenuation of the tube formation in hypoxic human umbilical vascular endothelial cells (HUVECs), and the vasculature generation in Matrigel plug, the chicken chorioallantoic membrane, and tumors. Treatment with AE-AS markedly decreased the protein accumulation and transcriptional activity of HIF-1α, vascular endothelial growth factor (VEGF) expression/secretion, and VEGFR2 phosphorylation in hypoxic human bladder cancer (T24) cells and tumor tissues accompanied by a reduction of tumor growth. Notably, AE-AS-induced HIF-1α protein degradation may, at least partly, attribute to inhibition of WSB-1-dependent pVHL degradation. Moreover, VEGFR2-activated PI3K/AKT/mTOR signaling pathway in hypoxic T24 cells was greatly inhibited by AE-AS. Collectively, AE-AS may be a potential anticancer agent by attenuating cancer angiogenesis via suppression of WSB-1/pVHL/HIF-1α/VEGF/VEGFR2 cascade.

In Vitro Anticancer Activity and Structural Characterization of Ubiquinones from Antrodia cinnamomea Mycelium.

Two new ubiquinones, named antrocinnamone and 4-acetylantrocamol LT3, were isolated along with six known ubiquinones from Antrodia cinnamomea (Polyporaceae) mycelium. The developed HPLC analysis methods successfully identified eight different ubiquinones, two benzenoids, and one maleic acid derivative from A. cinnamomea. The ubiquinones 1-8 exhibited potential and selective cytotoxic activity against three human cancer cell lines, with IC50 values ranging from 0.001 to 35.883 µM. We suggest that the different cytotoxicity levels were related to their chemical structures, especially the 4-hydroxycyclohex-2-enone ring and the presence of a free hydroxyl group in the side chain. The suppression by 4-acetylantrocamol LT3 stopped the cell cycle at the beginning of the G2-M phase thus making the cell cycle arrest at the sub-G1 phase as compared with control cells.

Corrigendum to "Ferulic Acid, an Angelica sinensis-Derived Polyphenol, Slows the Progression of Membranous Nephropathy in a Mouse Model".

[This corrects the article DOI: 10.1155/2012/161235.].

[Correlation between the expression of Pim-1 and androgen-deprivation therapy for prostate cancer].

OBJECTIVE: To investigate the expression of the Pim-1 gene in the LNCaP cells of the animal model of orthotopically implanted prostate cancer by surgical castration simulating androgen-deprivation therapy. METHODS: We equally allocated 32 male BALBc-nu mice into 4 groups, androgen-dependent prostate cancer (ADPC), androgen-deprivation therapy (ADT) , castration-resistant prostate cancer (CRPC) and blank control, and established the models of orthotopically implanted tumor using human prostate cancer LNCaP cells. We detected and ,compared the expressions of Pim-1, PSA, and androgen receptor (AR) in the tumor tissues of different groups by RT-PCR. qRT-PCR, ELSIA and immunohistochemistry. RESULTS: The relative gray scales in the ADPC and CRPC groups were 0.59 ± 0.01 and 1.14 ± 0.02, with statistically significant differences from 0.62 ± 0.03 in the ADT group (P < 0.05), and the Δ Ct values of Pim-1 were 6.15 ± 0.34 and 4.56 ± 0.23 in the former two groups, also with significant differences from 5.11 ± 0.21 in the latter (P < 0.05). The results of 2-ΔΔ Ct relative quantification analysis showed that the amplification products of Pim-1 in the ADT and CRPC groups increased 2.05 and 3.01 times respectively that of the ADPC group. The concentration of PSA was significantly higher in the ADPC ([480 ± 25] pg/ml) and CRPC ([870 ± 23] pg/ml) than in the ADT ([170 ± 32] pg/ml) and blank control groups (0 µg/L) (P < 0.01). The mean optical densities of Pim-1 and AR proteins were 0.017 ± 0.002 and 0.032 ± 0.009 in the ADPC group and 0.024 ± 0.002 and 0.040 ± 0.011 in the CRPC group, both with significant differences from those in the ADT group (0.018 ± 0.001 and 0.019 ± 0.006) (P < 0.01). CONCLUSION: Pim-1 is highly expressed in nude mice with prostate cancer receiving androgen-deprivation therapy and plays an important role in the progression and metastasis of prostate cancer.

Anti-cancer agents derived from solid-state fermented Antrodia camphorata mycelium.

Three new ubiquinone derivatives, antrocamol LT1, antrocamol LT2, and antrocamol LT3, along with two known compounds, were isolated from Antrodia camphorata (Polyporaceae) mycelium. The structures of these compounds were established on the basis of extensive 1D and 2D NMR spectroscopic analyses. These ubiquinones exhibited selective cytotoxicities against five human cancer cell lines (CT26, A549, HepG2, PC3 and DU-145) with IC50 values ranging from 0.01 to 1.79µΜ.

Cytotoxic effect of triterpenoids from the root bark of Hibiscus syriacus.

In this study, 4 new triterpenoids-3ß- acetoxy-olean-11-en,28,13ß-olide (1), 3ß- acetoxy-11α,12α-epoxy-olean-28,13ß-olide (2), 19α-epi-betulin (3), and 20, 28-epoxy-17ß,19ß-lupan-3ß-ol (4)-and 12 known compounds, were isolated from the root bark of Hibiscus syriacus L. by using acetone extraction. Their structures were characterized by extensive spectroscopic analysis. To investigate cytotoxicity, A549 human lung cancer cells were exposed to the extract and the compounds identified from it. Significantly reduced cell viability was observed with betulin-3-caffeate (12) (IC50, 4.3 µM). The results of this study indicate that betulin-3-caffeate (12) identified from H. syriacus L. may warrant further investigation for potential as anticancer therapies.

Ovatodiolide Targets ß -Catenin Signaling in Suppressing Tumorigenesis and Overcoming Drug Resistance in Renal Cell Carcinoma.

Dysregulated ß -catenin signaling is intricately involved in renal cell carcinoma (RCC) carcinogenesis and progression. Determining potential ß -catenin signaling inhibitors would be helpful in ameliorating drug resistance in advanced or metastatic RCC. Screening for ß -catenin signaling inhibitors involved in silico inquiry of the PubChem Bioactivity database followed by TCF/LEF reporter assay. The biological effects of ovatodiolide were evaluated in 4 RCC cell lines in vitro and 2 RCC cell lines in a mouse xenograft model. The synergistic effects of ovatodiolide and sorafenib or sunitinib were examined in 2 TKI-resistant RCC cell lines. Ovatodiolide, a pure compound of Anisomeles indica, inhibited ß -catenin signaling and reduced RCC cell viability, survival, migration/invasion, and in vitro cell or in vivo mouse tumorigenicity. Cytotoxicity was significantly reduced in a normal kidney epithelial cell line with the treatment. Ovatodiolide reduced phosphorylated ß -catenin (S552) that inhibited ß -catenin nuclear translocation. Moreover, ovatodiolide decreased ß -catenin stability and impaired the association of ß -catenin and transcription factor 4. Ovatodiolide combined with sorafenib or sunitinib overcame drug resistance in TKI-resistant RCC cells. Ovatodiolide may be a potent ß -catenin signaling inhibitor, with synergistic effects with sorafenib or sunitinib, and therefore, a useful candidate for improving RCC therapy.

Association of the polymorphism of APE1 gene with the risk of prostate cancer in Chinese Han population.

BACKGROUND: DNA damage, caused by numerous carcinogens, contributes to the increased risk of different types of cancer. The base excision repair (BER) pathway including the apurinic/apyrimidic endonuclease (APE1, also known as APEX1) gene plays an important role in preventing the accumulation of DNA damage and maintaining genomic stability. The aim of the present study is to determine whether polymorphisms of APE1 are associated with the risk of prostate cancer (PCa) in the Chinese Han population. METHODS: This study consisted of 198 patients with PCa and 156 healthy controls. The polymorphisms of APE1, Asp148Glu (rs1130409) and -141T/G (rs1760944) were determined by the polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) method. RESULTS: The genotypic distributions of the two polymorphisms in controls were in Hardy-Weinberg equilibrium (p = 0.92 and p = 0.83, respectively). Logistic regression analysis indicated that the -141GG genotype was significantly associated with a decreased risk of PCa compared with the -141TT genotype (p = 0.03; OR 0.49; 95% CI 0.26 - 0.92). The G allele was also significantly associated with a reduced risk of PCa compared with the T allele (p = 0.02; OR 0.71; 95% CI 0.52 - 0.96). However, no association between Asp148Glu polymorphism and the risk of PCa was found. CONCLUSIONS: The -141GG genotype and G allele of the APE1 gene are associated with a decreased risk of PCa in the Chinese Han population.

A novel mechanism underlies the hepatotoxicity of pyrazinamide.

Relatively little is known about the hepatotoxicity of pyrazinamide (PZA). PZA requires activation by amidase to form pyrazinoic acid (PA). Xanthine oxidase then hydroxylates PA to form 5-hydroxypyrazinoic acid (5-OH-PA). PZA can also be directly oxidized to form 5-OH-PZA. Before this study, it was unclear which metabolic pathway or PZA metabolites led to hepatotoxicity. This study determines whether PZA metabolites are responsible for PZA-induced hepatotoxicity. PZA metabolites were identified and cytotoxicity in HepG2 cells was assessed. Potential PZA and PA hepatotoxicity was then tested in rats. Urine specimens were collected from 153 tuberculosis (TB) patients, and the results were evaluated to confirm whether a correlation existed between PZA metabolite concentrations and hepatotoxicity. This led to the hypothesis that coadministration of amidase inhibitor (bis-p-nitrophenyl phosphate [BNPP]) decreases or prevents PZA- and PZA metabolite-induced hepatotoxicity in rats. PA and 5-OH-PA are more toxic than PZA. Electron microscopy showed that PZA and PA treatment of rats significantly increases aspartate transaminase (AST) and alanine aminotransferase (ALT) activity and galactose single-point (GSP) levels (P < 0.005). PA and 5-OH-PA levels are also significantly correlated with hepatotoxicity in the urine of TB patients (P < 0.005). Amidase inhibitor, BNPP, decreases PZA-induced, but not PA-induced, hepatotoxicity. This is the first report of a cell line, animal, and clinical trial confirming that the metabolite 5-OH-PA is responsible for PZA-induced hepatotoxicity.

Ferulic Acid, an Angelica sinensis-Derived Polyphenol, Slows the Progression of Membranous Nephropathy in a Mouse Model.

Membranous nephropathy (MN) is a leading cause of adult nephrotic syndrome but lacks adequate treatment. Different extracts of Angelica sinensis (AS) and one of its active compounds, ferulic acid (FA), were used to evaluate the therapeutic effects in a MN mouse model. The MN model was grouped into three subgroups: no treatment (N-T), treatment at induction of MN (Pre-T), and treatment after full-blown MN (Post-T). The results showed that the methanol (ME) layer of AS extract exhibited a therapeutic effect on MN-induced proteinuria. The ME layer-enriched compound, FA, improved the hypoalbuminemia, hyperlipidemia, and proteinuria in both Pre-T and Post-T groups. Ferulic acid also reduced the formation of oxidative protein products and increased the synthesis of antioxidant enzymes in groups Pre-T and Post-T. Regarding angiogenesis factors, the antiangiogenic factors in renal glomeruli were increased in group N-T, but, after FA treatment, only one of the antiangiogenic factors, thrombospondin-1, showed a significant decrease. Furthermore, the expression of Th2 predominant showed significant decrease in both Pre-T and Post-T groups when compared to that of N-T group. In summary, FA retarded the progression of MN, and the mechanisms involved the regulation of oxidative stresses, angiogenic and antiangiogenic factors, and attenuation of Th2 response.

[Undifferentiated prostate sarcoma with cartilage metaplasia: a case report and review of the literature].

OBJECTIVE: To investigate the clinical presentations and pathologic features of undifferentiated sarcoma of the prostate with cartilage metaplasia, and to clarify its category. METHODS: We analyzed the clinical data of a case of undifferentiated sarcoma of the prostate with cartilage metaplasia treated by surgical resection. The tumor tissue was subjected to routine HE and immunohistochemical staining, its histological structure and immunohistochemical expression were observed under the light microscope, and relevant literature on its manifestations was reviewed. RESULTS: The case was pathologically diagnosed as gray prostate tumor, with chondrosarcomatous and undifferentiated malignant mesenchymal components under the light microscope. Immunohistochemical staining revealed vimentin (+), local CD117 (+/-), SMA (-), Des (-), myoglobin (-), CD34 (-), CK7 (-), and CK8 (-). Tumor metastasis was found 2 months after the operation, and the patient died 4 months later. CONCLUSION: Undifferentiated sarcoma of the prostate with cartilage metaplasia is a very rare and highly malignant aggressive tumor, which can be diagnosed by biopsy and immunohistochemistry.

[Prostate cancer with five different histological features: a case report and review of the literature].

OBJECTIVE: To study the clinical manifestations, pathological characteristics and treatment methods of prostate cancer with five different histological features. METHODS: We reported 1 case of prostate cancer with five different histological features and further analyzed the diagnosis, pathology and treatment of the disease by reviewing the relevant literature. RESULTS: The patient was an 84-year-old male, admitted due to difficult urination and dribbling urine for 1 year, hematuria for 8 months and deterioration for 2 weeks. Prostate cancer was indicated by rectal examination, ultrasonography, CT, MRI and PSA, and confirmed by biopsy. Considering the general condition of the patient, we performed electrotransurethral resection under epidural anesthesia to alleviate his urinary symptoms and remove suspected tumor tissues. Postoperative pathology showed the case to be prostate adenocarcinoma, histologically characterized by cribriform carcinoma, acinar carcinoma, diffuse invasive carcinoma, ductal carcinoma, and mucinous adenocarcinoma, with a Gleason score of 9. Bicalutamide and goserelin were administered postoperatively. Systemic metastasis occurred 10 months later, and the patient died 1 year after the operation. CONCLUSION: Prostate cancer with five different histological features is extremely rare. Its early diagnosis is difficult and mainly depends on pathological and immunohistochemical examinations, and radical prostatectomy can be considered for its treatment.

Epigallocatechin-3-gallate prevents lupus nephritis development in mice via enhancing the Nrf2 antioxidant pathway and inhibiting NLRP3 inflammasome activation.

Patients with lupus nephritis show an impaired oxidative status and increased levels of interleukin (IL)-1ß and IL-18, which are closely linked to inflammation and correlated with disease activity. Although epigallocatechin-3-gallate (EGCG), the major bioactive polyphenol present in green tea with antioxidant and free radical scavenging activities, has been reported to have anti-inflammatory effects by inhibiting nuclear factor-kappa B (NF-κB)-mediated inflammatory responses in vivo, its effectiveness for the treatment of lupus nephritis is still unknown. In the present study, 12-week-old New Zealand black/white (NZB/W) F1 lupus-prone mice were treated daily with EGCG by gavage until sacrificed at 34 weeks old for clinical, pathological, and mechanistic evaluation. We found that the administration (1) prevented proteinuria, renal function impairment, and severe renal lesions; (2) increased renal nuclear factor E2-related factor 2 (Nrf2) and glutathione peroxidase activity; (3) reduced renal oxidative stress, NF-κB activation, and NLRP3 mRNA/protein expression and protein levels of mature caspase-1, IL-1ß, and IL-18; and (4) enhanced splenic regulatory T (Treg) cell activity. Our data clearly demonstrate that EGCG has prophylactic effects on lupus nephritis in these mice that are highly associated with its effects of enhancing the Nrf2 antioxidant signaling pathway, decreasing renal NLRP3 inflammasome activation, and increasing systemic Treg cell activity.

Phytoestrogen bavachin mediates anti-inflammation targeting Ikappa B kinase-I kappaB alpha-NF-kappaB signaling pathway in chondrocytes in vitro.

The pro-inflammatory cytokine interleukin-1 beta (IL-1 beta) plays critical roles in pathogenesis of osteoarthritis. Although estrogen is protective for cartilage in osteoarthritis patients, it also potentially increases the risk of stroke and cancer. Phytoestrogens acting as natural estrogen receptor modulators may serve as alternatives. This study aimed to identify medicinal phytoestrogens that preserve anti-inflammatory property and may function as potential chondro-protective compounds. Both human chondrocytes and chondrocytic cell line CHON-002 were used for this study. Protein concentrations or expressions were measured by ELISA or Western blot, respectively. The DNA-binding activity and transcriptional activity of transcription factors were evaluated by electrophoretic mobility shift assay and dual-luciferase reporter assay, respectively. Cell migration was analyzed by chemotaxis assays. We found that among screened phytoestrogens, bavachin could potently decrease IL-1 beta-induced nuclear factor-kappa B (NF-kappaB) but not activator protein-1 (AP-1) DNA-binding activity. Bavachin also inhibited I kappaB alpha degradation, increased nuclear translocation of p65 and p50 as well as decreased I kappaB alpha kinase (IKK) activity. Furthermore, bavachin inhibited IL-1 beta-induced chemokine production that resulted in reduced migration of THP-1 monocytic cells. Our results suggest that through decreasing IL-1 beta-induced activation of IKK-I kappaB alpha-NF-kappaB signaling pathway, bavachin potentially protects cartilage from inflammation-mediated damage in joints of osteoarthritis patients.

The induction of orphan nuclear receptor Nur77 expression by n-butylenephthalide as pharmaceuticals on hepatocellular carcinoma cell therapy.

N-butylidenephthalide (BP), isolated from the chloroform extract of Angelica sinensis, has been examined for its antitumor effects on glioblastoma multiforme brain tumors; however, little is known about its antitumor effects on hepatocellular carcinoma cells. Two hepatocellular carcinoma cell lines, HepG2 and J5, were treated with either N-butylidenephthalide or a vehicle, and cell viability and apoptosis were evaluated. Apoptosis-related mRNA and proteins expressed, including orphan receptor family Nurr1, NOR-1, and Nur77, were evaluated as well as the effect of N-butylidenephthalide in an in vivo xenograft model. N-butylidenephthalide caused growth inhibition of both the cell lines at 25 microg/ml. Furthermore, N-butylidenephthalide-induced apoptosis seems to be related to Nur77 translocation from nucleus to cytosol, which leads to cytochrome c release and caspase-3-dependent apoptosis. N-butylidenephthalide-related tumor apoptosis was associated with phosphatidylinositol 3-kinase/protein kinase B (AKT)/glycogen synthase kinase-3beta rather than the mitogen-activated protein kinase or protein kinase C pathway. Blockade of AKT activation enhanced proliferation inhibition and the induction of phosphor-Bcl-2 and Nur77 proteins. Besides, the increasing apoptosis by BP via transfection wild-type cAMP-response element-binding protein (CREB) into tumor cell was suppressed by dominant phosphorylation site mutation of CREB. This finding suggested CREB pathway was also partly involved in tumor apoptosis caused by BP. Administration of N-butylidenephthalide showed similar antitumoral effects in both HepG2 and J5 xenograft tumors. N-Butylidenephthalide induced apoptosis in hepatocellular carcinoma cells, both in vitro and in vivo, suggesting a potential clinical use of this compound for improving the prognosis of hepatocellular carcinoma cells.

Orphan nuclear receptor, Nurr-77 was a possible target gene of butylidenephthalide chemotherapy on glioblastoma multiform brain tumor.

The natural compound n-butylidenephthalide (BP), which is isolated from the chloroform extract of Angelica sinensis, has been investigated for its antitumoral effects on glioblastoma multiform (GBM) brain tumors both in vitro and in vivo. To determine the mechanism of BP-induced growth arrest and apoptosis, we examined BP-induced changes in gene expression by microarray screening using human GBM brain tumor cells. This analysis identified several BP-inducible genes, including the nuclear receptors NOR-1, Nurr1, and Nur77. Among these genes, Nur77 is particularly interesting because it plays an important role in the apoptotic processes in various tumor cell lines. BP was able to increase Nur77 mRNA and protein expression in a time-dependent manner. After BP treatment in GBM 8401 cells, Nur77 translocated from the nucleus to the cytoplasm, the cytochrome c was released from the mitochondria, and caspase 3 became activated. Furthermore, using Nur77 promoter-luciferase assay, BP increased Nur77 was AP1 related. Inhibition of BP-induced Nur77 expression by Nur77 short interfering RNA blocked BP-induced apoptosis in GBM 8401 cells, suggesting that the induction of Nur77 negatively affected GBM 8401 cell survival. In summary, our results suggest that up-regulation of Nur77 may explain the antitumoral activity of BP in brain tumor cells.

The extract of Hibiscus syriacus inducing apoptosis by activating p53 and AIF in human lung cancer cells.

Natural products including plants, microorganisms and marine life provide rich resources for anticancer drug discovery. The root bark of Hibiscus syriacus has been used as an antipyretic, anthelmintic and antifungal agent in Asia. The antiproliferative effects of H. syriacus on human lung cancer cells were evaluated with bio-assays. The apoptotic activity was detected by Hoechst 33342 DNA staining and annexin V staining. The expression of caspases, p53, apoptosis induced factor (AIF), Bcl-2 and Bax were evaluated with Western blotting. The in vivo anticancer activity was evaluated using A549-xenograft model. The acetone extract of H. syriacus (HS-AE) exhibited a better cytotoxic effect on lung cancer cells than its methanol extract (HS-ME) or water extract (HS-WE). The IC(50) values of HS-AE on A549 (adenocarcinoma), H209 (squamous cell carcinoma) or H661 (large cell carcinoma) lung cancer cells ranged from 14 to 22 microg/ml after 48 hours of treatment. After 48 hours of exposure, HS-AE (15 microg/ml) induced A549 cell apoptosis to 48 +/- 3.6% of the control. Using Western blotting, HS-AE appears to suppress the expression of p53 and AIF. The results of the in vivo study showed that HS-AE suppresses growth in A549 subcutaneous xenograft tumors. These results indicate that HS-AE exerts significant and dose-dependent antiproliferative effects on cancer cells in vitro and in vivo, which prompts us to further evaluate and elucidate the bioactive component(s) of H. syriacus.