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Triple-negative breast cancer (TNBC) is a subtype of breast cancer with high mortality and poor prognosis. Meanwhile, doxorubicin, a chemotherapeutic agent for triple-negative breast cancer, has poor sensitivity. The objective of this study was to examine the effect of cordycepin on doxorubicin sensitivity and efficacy in the TNBC xenograft model and explore the relevant molecular pathways. The combination of the drugs in nude mice carrying MDA-MB-231 xenografts significantly reduced the volume, size, and weight of xenografts and improved the tumor inhibition rate. The drug combination was significantly more effective than cordycepin or doxorubicin alone, reflecting the fact that cordycepin enhanced the anti-tumor effects of doxorubicin in MDA-MB-231 xenografts. At the same time, the monitoring of several biological parameters failed to detect any obvious side effects associated with this treatment. After predicting the importance of the TNF pathway in inhibiting tumor growth using network pharmacology methods, we verified the expression of TNF pathway targets via immunohistochemistry and quantitative PCR. Furthermore, a TNF-α inhibitor was able to abrogate the beneficial effects of cordycepin and doxorubicin treatment in MDA-MB-231 cells. This clearly indicates the role of TNF-α, or related molecules, in mediating the therapeutic benefits of the combined treatment in animals carrying TNBC xenografts. The observations reported here may present a new direction for the clinical treatment of TNBC.

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Sanghuangporus sanghuang is a rare fungus growing on mulberry trees that has immense medicinal value. This study aimed to optimize the liquid-fermentation-media formulation and culture conditions for large-scale culturing of S. sanghuang by performing one-way testing and response surface methodology. The antioxidant and anticancer activities of the extracellular polysaccharides from S. sanghuang were also analyzed. The optimal formulation and growth conditions for S. sanghuang were as follows: glucose, 30.2 ± 0.37 g/L; yeast extract, 14.60 ± 0.05 g/L; dandelion powder, 1.24 ± 0.01 g/L; shaker speed, 150 r/min; and temperature, 25 °C. We obtained 13.99 ± 0.42 g/L of mycelium biomass by culturing S. sanghuang for 15 days with the optimized formulation. This was 2-fold higher than the mycelial mass obtained with the sub-optimal formulation. The extracellular fungal polysaccharides showed significant antioxidant activity against ABTS and DPPH free radicals, and significantly reduced the in vitro growth and survival of several cancer cell lines. The anticancer activity of the extracellular fungal polysaccharides was significantly higher in the human glioma cells than in other cancer cell lines. In summary, this study optimized the liquid media formulation and conditions for the large-scale culturing of S. sanghuang. Furthermore, the extracellular polysaccharides from S. sanghuang showed significant antioxidant and anticancer activities.

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SCOPE: Alcoholic liver disease (ALD) is a common disease with a high incidence. Because traditional drugs have obvious side effects, it is desired to find more effective drugs. METHODS AND RESULTS: This study investigates the effects of melanin from Inonotus hispidus fruiting bodies (IHFM) on acute alcoholic injury mice and detects the protective mechanisms via the gut-microbiota-liver axis. The results show that IHFM alleviates mouse liver injury by enhancing alcohol metabolism capacity, reducing inflammation response level and strengthening antioxidant activities. IHFM also improves mouse liver injury by activating Nrf2 signaling pathway and inhibiting toll-like receptor4 (TLR4)/nuclear factor-κß (NF-κß) signaling pathway. Furthermore, 16S amplification sequencing shows that IHFM can significantly increase the relative abundance of Lactobacillus reuteri and Lactobacillus johnsonii. The relative abundance of L. reuteri positively correlates with an antioxidant index, while negatively correlates with inflammatory factors. CONCLUSION: IHFM can protect mice from acute alcoholic liver injury by upregulating the Nrf2 signaling pathway, downregulating the TLR4/NF-κß signaling pathway, and upregulating the relative abundance of L. reuteri and L. johnsonii, representing a step forward in the development of IHFM.

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Gelsemiumelegans(Gardner. & Chapm.) Benth. has long been considered a traditional Chinese medicine effective against rheumatoid pain, cancer, cirrhosis, and skin diseases. Koumine (KM), the most abundant alkaloid in G.elegans Benth., demonstrates a variety of biological effects, including antitumor, analgesic, anxiolytic, anti-inflammatory, antidepressant, antioxidant, immunoregulatory, and hepatoprotective effects. Furthermore, the relatively low toxicity of KM makes it a promising drug candidate. This study aimed to investigate the protective effects of KM and its possible mechanisms using a concanavalin A (Con A)-induced autoimmune hepatitis (AIH) model in mice. Mice were orally administered different doses of KM for 14 d before Con A tail vein injections. The effects of KM on serum biochemical markers and liver histopathology were then evaluated 12 h after Con A exposure. The Nrf2 and NF-κB signaling pathways and alterations in gut microbiota were determined using western blotting, immunohistochemistry, and 16S rRNA sequencing to explore the underlying mechanisms of KM exposure. KM pretreatment dose-dependently decreased serum liver injury markers (Alanine aminotransferase, and aspartate aminotransferase) and cytokine levels (Tumor necrosis factor-α and interleukin-6), as well as the liver pathological damage triggered by Con A. Furthermore, the results of the multi-technique analysis indicated that KM activated the Nrf2 pathway, upregulated the expression of anti-oxidation factors HO-1 and Nrf2, and downregulated the expression of Keap1. Moreover, the NF-κB signaling pathway was inhibited. Interestingly, pre-treatment with KM also significantly improved the composition of the gut microbiota probably because it increases the richness of probiotics. Our findings suggest that KM pretreatment could attenuate Con A-induced AIH, the Nrf2 and NF-κB signaling pathways, and that gut microbiota are involved in the process of the hepatoprotective effect. This study provides a theoretical basis for the development of KM as an effective agent against AIH.

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Melanin is a natural pigment with a high content and a complex polymer structure. In this study, both water-soluble and water-insoluble melanin were obtained from the fruiting bodies of the mushroom Inonotus hispidus, and scanning electron microscopy (SEM), ultraviolet (UV) absorption, Fourier transform infrared (FTIR) spectroscopy, elemental analysis, nuclear magnetic resonance (NMR) spectroscopy, pyrolysis gas chromatography mass spectroscopy (Py-GCMS), and matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF-MS/MS) were used to analyze the water-soluble and water-insoluble I. hispidus fungal melanin (IHFM). Differences in the chemical composition and structure of I. hispidus fungal melanin (IHFM) were found. Studies showed that both have a maximum absorbance at 226 nm, and the maximum mass-to-charge ratios are [M + H] + m/z = 272.2434 and 272.0308, respectively. Elemental analysis revealed that they both contain C, H, N, O, and do not contain sulfur, which is only found in eumelanin. The differences between water-soluble and water-insoluble IHFM may relate to the following factors: (i) the microscopic particles of water-soluble IHFM are relatively small, the arrangement is relatively neat, and they contain a large quantity of benzene, phenol, and indole compounds; and (ii) the microscopic particles of water-insoluble IHFM are larger and the arrangement is irregular. The types and quantities of benzene, phenol, and indole compounds are relatively small, rich in a variety of sugar monomers, and may be insoluble in water due to the presence of a greater number of aliphatic groups. Studies have found that water-soluble IHFM has good cellular antioxidant activity, can reduce oxidative damage by hydrogen peroxide (H2O2) on LO2 cells effectively and can significantly reduce the level of intracellular reactive oxygen species (ROS) to protect the liver. These results are beneficial in order to develop applications of melanin in the food industry and in other fields.

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We previously found that cordycepin inhibits the growth and metastasis formation of MDA-MB-231 cells through the Hedgehog pathway but has not validated this in vivo. In this study, we confirmed cordycepin's anti-triple-negative breast cancer (TNBC) effect in nude mice and documented its mechanism. We found that cordycepin reduced the volume and weight of MDA-MB-231 xenografts and affected the expression of proliferation-, apoptosis-, epithelial-mesenchymal transition-, and matrix metalloproteinase-related proteins without side effects. RNA sequencing screening, pathway enrichment, and the protein network interaction analysis revealed enriched pathways and targets mainly concentrated on the Hedgehog pathway and its core components of SHH and GLI2. This indicates that the Hedgehog pathway plays a central role in the cordycepin-mediated regulation of growth and metastasis formation in TNBC. The database analysis of the Hedgehog pathway markers (SHH, PTCH1, SMO, GLI1, and GLI2) revealed that the Hedgehog pathway is activated in breast cancer tissues, and its high expression is not conducive to a patient's survival. Finally, we verified that cordycepin effectively inhibited the Hedgehog pathway in TNBC through Western blotting and immunohistochemistry. This study found that cordycepin could regulate the growth and metastasis formation of TNBC through the Hedgehog pathway in vivo, which provides new insights for targeting and treating breast cancer.

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Polysaccharides have high antioxidant, hypoglycemic, hypolipidemic, hepatoprotective, anti-tumor, and anticancer activities. In this study, the ability of the Lyophyllum decastes fruiting body polysaccharide (LDFP) to protect against CCl4-induced acute liver injury in mice by activating the Nrf2 pathway was studied. LDFP can inhibit the activity of ALT, AST, TC, TG, tumor necrosis factor (TNF-α), and interleukin-6 (IL-6) in serum; significantly improve the inflammatory state of the liver; increase the activity of superoxide dismutase (SOD) and the glutathione (GSH) content; decrease the malondialdehyde (MDA) content; alleviate the toxicity caused by reactive oxygen species; and alleviate liver injury. Immunohistochemistry and western blot showed that LDFP can activate the Nrf2 pathway, up-regulate the expression of Nrf2, down-regulate the expression of Keap1, and increase the expression of the anti-oxidation factors HO-1 and CuZn-SOD. At the same time, it was found that the expression of the transcription factors TLR-4 and NF-κB were decreased in the NF-κB signaling pathway, the synthesis and secretion of the pro-inflammatory factors IL-6 and TNF-α were decreased consequently. These results suggest that LDFP protects the liver by activating the Nrf2 pathway and reducing the inflammatory response. Generally, the results of this study could be used to aid the development of hepatoprotective products and their application.

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Melanin has good nutritional and medicinal value; however, its extraction rate is extremely low. This study explored the edible and medicinal fungus Inonotus hispidus fruiting body melanin (IHFM) extraction process and solid-state fermentation conditions. The results showed that the best way to extract IHFM is the compound enzymatic method, with complex enzyme 26.63 mg/g, liquid material ratio 5:1, enzymatic hydrolysis 80 min, pH 4.61, and enzymolysis temperature at 36.07 °C. The yield of IHFM was 23.73 ± 0.57%, which was equivalent to 1.27 times before optimization. The best solid medium formula was normal pH, rice 20 g per cultivation bottle, maltose 22 g/L, beef extract 4.4 g/L, carbon-nitrogen ratio 5:1, and liquid-to-material ratio 1.1:1, where the IHFM yield was 31.80 ± 1.34%, which was equivalent to 1.7 times that before optimization. In summary, solid-state fermentation and extraction optimization greatly improved the yield of melanin, provided a reference to produce melanin, and laid a foundation for the development and utilization of melanin.

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In the study, we investigated the role of the hedgehog (Hh) pathway in cordycepin's effects on human breast cancer cells, with respect to cell growth, apoptosis and metastasis. We found cordycepin to have low toxicity but significant anticancer effects. Cordycepin-induced apoptosis led to increased PUMA, CYTO-C, FAS, DR4/5, and cleaved caspase-3; and decreased BCL-2, XIAP and PDGFR-α. Cordycepin inhibited metastasis, which was associated with up-regulated E-cadherin, and down-regulated N-cadherin, SNAIL, SLUG and ZEB1. Cordycepin also inhibited expression of Hh pathway components and GLI transcriptional activity. Inversely, knockout of GLI blocked cordycepin-mediated effects on the apoptotic, epithelial-mesenchymal transition (EMT) and Notch pathways, which indicates that GLI is crucial for cordycepin's effects against breast cancer. Inhibition of GLI enhanced cordycepin's effect on breast cancer cell growth. To our knowledge, this is the first study of cordycepin's effect on the Hh pathway in breast cancer, and provides preliminary data for the in vivo study, and possible therapeutic use, of cordycepin.

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In order to promote the comprehensive utilization of the Auricularia auricula waste residue, the extraction process and the physicochemical properties of melanin from A. auricula waste residue were studied. Furthermore, the chemical antioxidant activity of waste residue melanin and its protective effect on cell oxidative injury induced by H2O2 were investigated. The results indicated that the ultrasonic-assisted extraction process could be used to extract the melanin from A. auricula waste residue. Melanin had a good solubility in alkali solution and exhibited a certain stability to thermal. There was no significant difference between A. auricula melanin control group and waste residue melanin on ABTS, DPPH, and hydroxyl radical scavenging activity. Waste residue melanin significantly inhibited the cell death caused by H2O2, and the cell viability was restored to 98.09 ± 5.97% when the melanin concentration was 1.6 mg/ml. Cell morphology observation confirmed that the melanin ameliorated the morphological changes of cells induced by oxidative stress.

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Cordyceps militaris exopolysaccharides (EPS) have many pharmacological activities such as boosting immunity and antifatigue. To obtain EPS efficiently, we added moderate Vernonia amygdalina leaf powder as inducer to the fermentation medium to promote the production of Cordyceps militaris EPS and studied the infrared absorption spectrum and antioxidant activities of the EPS after optimization. The optimum liquid fermentation conditions were as follows: addition of Vernonia amygdalina leaf powder of 8 g/L, fermentation duration of 9 d, initial pH of 6.5, inoculation quantity of 5.0 mL. Under such a condition, the yield of Cordyceps militaris EPS reached (5.24±0.28) mg/mL, increased by 205.20% compared to the control group without adding Vernonia amygdalina leaf powder. Results of infrared analysis and antioxidant activity showed that the Vernonia amygdalina leaves had little effect on the structure and activities of Cordyceps militaris EPS. The results of this research suggest that Vernonia amygdalina leaf can enhance the production of Cordyceps militaris EPS effectively, and provides a novel method for efficient production of EPS in Cordyceps militaris.

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Trans­3,4',5­trihydroxystilbene (resveratrol) is a naturally occurring polyphenolic phytoalexin with marked anticancer activities, and is mainly found in grapes, berries and peanuts. However, due to a low bioavailability, it has not progressed to clinical practice for cancer treatment. Therefore, the aims of the present study were to examine the anticancer activities of the resveratrol derivative, triacetyl resveratrol (TCRV), in pancreatic cancer cells. Apoptosis was measured by fluorescence­activated cell sorting and terminal deoxynucleotidyl transferase (TdT)­mediated dUTP nick­end labeling assays. Gene expression was measured by reverse transcription­quantitative polymerase chain reaction. TCRV inhibited colony formation and induced apoptosis through caspase­3 activation in human pancreatic cancer AsPC­1 and PANC­1 cells, whereas it exerted no effect on human pancreatic normal ductal epithelial cells (HPNE). TCRV inhibited epithelial­mesenchymal transition (EMT) by upregulating the expression of E­cadherin and suppressing the expression of N­cadherin and the transcription factors, Snail, Slug and Zeb1. TCRV inhibited Zeb1 3'UTR­luciferase activity through the upregulation of microRNA (miR)­200 family members. The inhibitory effects of TCRV on pancreatic cancer cell migration and invasion were counteracted by anti­miR­200 family members. The inhibitory effects of TCRV on EMT and the induction of apoptosis were exerted through the suppression of the sonic hedgehog (Shh) pathway, and through the modulation of cyclin D1 and Bcl­2 expression. The hyperactivation of the Shh pathway by either Shh protein or Gli1 overexpression abrogated the biological effects of TCRV. Taken together, the results of this study demonstrate that TCRV inhibits pancreatic cancer growth and EMT by targeting the Shh pathway and its downstream signaling mediators. TCRV inhibited EMT through the upregulation of miR­200 family members. Since TCRV effectively inhibited the growth of human pancreatic cancer cells by modulating the Shh pathway, without affecting the growth of HPNE cells, our findings suggest the possible use of TCRV as a promising candidate for the treatment and/or prevention of pancreatic cancer.

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This study characterized the Inonotus hispidus extracellular exopolysaccharide (IHEPS) from fermentation broth and investigated its liver protective effect on acute alcoholic liver injury in mice. The characterization of IHEPS was analyzed by HPLC, UV-vis and FT-IR. To determine the liver protective effect of IHEPS, mice were administered with IHEPS once daily for 3 weeks, before ethanol induced acute alcoholic liver injury. Biochemical parameters of liver function, histopathological sections, mRNA and protein expression of related antioxidant enzymes were compared between with or without IHEPS administrated mice. As a result, IHEPS could extend the duration of righting reflex, shorten the durations of the recovery, and decrease the liver index in acute alcoholic liver mice. At the same time, alanine aminotransferase (ALT), aspartate aminotransferase (AST), and malondialdehyde (MDA) levels were decreased in IHEPS mice. Moreover, increased alcohol dehydrogenase (ADH), catalase (CAT) and superoxide dismutase (SOD) levels were also found in IHEPS mice. Furthermore, IHEPS activated Nrf2 signaling pathway and increased the expression of downstream related antioxidant enzymes, such as NQO1, CAT and Cu-Zn SOD.

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This study characterized the natural melanin from Auricularia auricula and investigated its hepatoprotective effect on mice with acute alcoholic liver injury. The characterization of the melanin was analyzed based on elemental analysis, gel permeation chromatography (GPC), UV-visible spectroscopy (UV-visible), infrared spectrum (IR) and nuclear magnetic resonance spectra (NMR). To determine the liver protective effect of Auricularia auricula melanin, mice were administered with the melanin once daily for 3 weeks before ethanol induced liver injury. Biochemical parameters of liver function, histopathological sections, mRNA and protein expression of antioxidant enzyme were compared between mice with or without the melanin administered. Results showed that A. auricula melanin was a eumelanin and the average molecular weight was 48.99 kDa. The melanin can protect the mice from ethanol-induced liver injury by extending the duration of the righting reflex, and shortening the duration of the recovery. The liver index, serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), γ-glutamyl transpeptidase (γ-GT) and liver malondialdehyde (MDA) levels in mice treated with the melanin were significantly decreased. At the same time, the levels of liver alcohol dehydrogenase (ADH), and antioxidase such as catalase (CAT), and superoxide dismutase (SOD) were increased. Its protective effect may be related to the activation of nuclear factor E2-related factor 2 (Nrf2) and its downstream antioxidant enzymes such as glutamate cysteine ligase catalytic (GCLC), glutamate cysteine ligase modifier (GCLM), and NADP(H) quinine oxidoreductase 1 (NQO-1). These results suggested that A. auricula melanin may be an effective strategy to alleviate alcohol-induced liver damage.

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In this study, solid-state fermentation was used to produce Inonotus hispidus melanin (IH melanin). Its physicochemical properties were characterized, and ultrasonic-assisted extraction was used to optimize its extraction process. Characterization techniques like elemental analysis and so on were used to identify melanin. The solubility, stability, and antioxidant activity were also measured. Furthermore, the extraction process of IH melanin was optimized. The results showed that the pigment could be defined as dihydroxy phenylalanine (DOPA)-melanin, it displayed irregular spherical and ellipsoidal structures with average size of 89.33 nm. Melanin has a specific stability and shows antioxidant activity. The optimal extraction parameters of melanin were a NaOH concentration of 0.56 mol/L, solid-liquid ratio of 1:50, ultrasonic power of 300 W, extraction temperature of 70 °C, and ultrasonic time of 70 min. This study was the first time that IH melanin was obtained. The results may be applied to health food or food additives.

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Mutations in the genes encoding nuclear factor (erythroid-derived 2)-like 2 (NRF2), Kelch-like ECH-associated protein 1 (KEAP1), and cullin 3 (CUL3) are commonly observed in human esophageal squamous cell carcinoma (ESCC) and result in activation of the NRF2 signaling pathway. Moreover, hyperactivity of the transcription factor Nrf2 has been found to cause esophageal hyperproliferation and hyperkeratosis in mice. However, the underlying mechanism is unclear. In this study, we aimed to understand the molecular mechanisms of esophageal hyperproliferation in mice due to hyperactive Nrf2. Esophageal tissues were obtained from genetically modified mice that differed in the status of the Nrf2 gene and genes in the same pathway (Nrf2-/-, Keap1-/-, K5Cre;Pkm2fl/fl;Keap1-/-, and WT) and analyzed for metabolomic profiles, Nrf2 ChIP-seq, and gene expression. We found that hyperactive Nrf2 causes metabolic reprogramming and up-regulation of metabolic genes in the mouse esophagus. One of the glycolysis genes encoding pyruvate kinase M2 (Pkm2) was not only differentially up-regulated, but also glycosylated and oligomerized, resulting in increased ATP biosynthesis. However, constitutive knockout of Pkm2 failed to inhibit this esophageal phenotype in vivo, and this failure may have been due to compensation by Pkm1 up-regulation. Transient inhibition of NRF2 or glycolysis inhibited the growth of human ESCC cells in which NRF2 is hyperactive in vitro In summary, hyperactive Nrf2 causes metabolic reprogramming in the mouse esophagus through its transcriptional regulation of metabolic genes. Blocking glycolysis transiently inhibits cell proliferation and may therefore have therapeutically beneficial effects on NRF2high ESCC in humans.

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A polysaccharide from Inonotus hispidus was prepared by solid-state fermentation (SSF), and an efficient ultrasound-assisted extraction method was used to optimize the extraction process of Inonotus hispidus solid-state fermentation polysaccharide (IHSFP). The optimal extraction parameters were as follows: solid-liquid ratio of 1:40, ultrasound time of 34 min, ultrasound power of 350 W and ultrasound temperature of 70 °C. The yield of IHSFP was 51.06 ±â€¯0.34% under the optimal conditions. Two types of polysaccharide fractions (IHSFP-1 and IHSFP-2) were isolated by DEAE-52 and Sephadex G-200 columns. IHSFP-2 had stronger antioxidant activity than IHSFP-1, and it can reduce H2O2-induced oxidative damage to cells in vitro. Therefore, the properties of IHSFP-2 were further characterized. The results showed that the molecular weight of IHSFP-2 was 14.44 kDa, it was composed of glucose (Glc), mannose (Man), galactose (Gal), glucuronic acid (GlcUA), galactosamine (GalN), arabinose (Ara) and ribose (Rib), and the contents of these monosaccharides were 51%, 21%, 20%, 3%, 2%, 2% and 1%, respectively. The results of this study may contribute to the efficient production of the polysaccharide of Inonotus hispidus, and provide new ideas for its application in functional foods and cosmetics.

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Colon cancer, one of the leading causes of cancer-associated deaths, is the target of choice for nutrition-based-prevention approaches because of the direct and early contact between the active compounds and the cancerous tissues. We previously reported alkylresorcinols (ARs) as the major active components in wheat bran against human colon cancer. Here, we further investigate the anticancer mechanisms of action of ARs. Our mechanistic studies indicated that AR C15 and AR C17 exert their anticancer activities in colon-cancer cells by inducing apoptosis through PUMA upregulation and mitochondrial-pathway activation, inducing cell-cycle arrest through p21 upregulation, and inhibiting proteasome activity and Mdm2 expression. This cascade of distinct mechanisms was linked to the consequent activation and accumulation of p53. The results of treatment with p53 inhibitor further confirmed that the p53 pathway might play a very important role in AR-induced apoptosis in colon-cancer cells. Altogether these results show that AR C15 and AR C17 can specifically activate the mitochondrial pathway of apoptosis and cause cell-cycle arrest and that inhibition of p53 greatly reduces the activation of this pathway.

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Aberrant reactivation of the Sonic Hedgehog (SHH) signaling pathway promotes prostate cancer (PC) growth and progression by regulating cancer-related genes through its downstream effectors GLI1 and GLI2. Therefore, targeting the SHH-GLI pathway provides an alternative approach to avoid cancer progression. The aim of this study was to delineate the underlying molecular mechanisms by which GDC-0449 (a SMO receptor inhibitor) and GANT-61 (a GLI transcription factor inhibitor) regulate cellular proliferation and self-renewal in human PC stem cells (ProCSCs). Inhibition of the SHH signaling pathway by GANT-61 induced apoptosis with more efficacy than by GDC-0449 in ProCSCs and PC cell lines. GLI1 and GLI2 expression, promoter-binding activity and GLI-responsive luciferase reporter activity were all decreased with either GDC-0449 or GANT-61 treatment. Expression of Fas, DR4, DR5, and cleavage of caspase-3 and PARP were increased, whereas levels of PDGFR-α and Bcl-2 were reduced. Double knockout of GLI1 and GLI2 using shRNA abolished the effects observed with either GDC-0449 or GANT-61 treatment. Collectively, our results showed that GANT-61 and GDC-0449 induced ProCSC apoptosis by directly or indirectly inhibiting the activities of the GLI family transcription factors, may enhance the efficacy of PC treatment.

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