Phenylpropanoids and lignoids from the whole plant of Vaccinium emarginatum and their cytotoxicity against prostate cancer cells.

One new naturally occurring quinone, 3',4'-dihydroxy-1,2,6-trimethoxy-[1,1'-biphenyl]-4(1H)-one (1), one new diarylpropane, emarginone A (2), and one new neolignan, emarginone B (3), along with eighteen known compounds have been isolated from the chemical investigation of the EtOAc-soluble fraction of the Vaccinium emarginatum whole plant methanolic extract. The new structures were elucidated by combined analysis of spectroscopic analytical methods and comparison with the literature data obtained from known analogues. In addition, the cytotoxicity of compounds 2, 4, and 14-20 against Du145 and PC-3 prostate cancer cell lines using MTT cell proliferation assay was evaluated. Compounds 2 and 19 showed most potent cytotoxicity against Du145 with IC50 values of 7.53 and 6.63 µg/mL, respectively. Furthermore, compounds 2, 17, and 19 also exhibited significant cytotoxicity against PC-3 with IC50 values ranging from 3.44-6.64 µg/mL.

Ganoderma tsugae suppresses the proliferation of endometrial carcinoma cells via Akt signaling pathway.

Ganoderma is one of the common medicinal mushrooms in traditional Chinese medicine. Previous researches have unveiled the multifaceted biological activity of Ganoderma extract. Ganoderma tsugae has been investigated the potential on curing prostate, colon, lung, epidermoid, breast and ovarian cancers, but not including endometrial cancer. Endometrial cancer is a gynecological malignant tumor with serious drug resistance problem in clinical cancer treatment. This study aimed to demonstrate the first study of Ganoderma on treating endometrial cancer. The Ganoderma tsugae ethanol extract (GTEE) could suppress the proliferation of endometrial cancer cells HEC-1-A, KLE, and AN3 CA. GTEE also induced G1/S phase arrest and mitochondria-mediated apoptosis in endometrial cancer cells. Furthermore, the Akt signaling pathway could be suppressed by GTEE. Therefore, our results suggest for the first time that GTEE has the potential to be an adjuvant therapeutic agent in the treatment of endometrial cancer.

Cytotoxic and Anti-inflammatory Terpenoids from the Whole Plant of Vaccinium emarginatum.

Two new Δ12 ursene-type triterpenoid coumaroyl esters (1: and 2: ), one new Δ7,15 isopimarane-type diterpenoid glycoside (20: ), and two new irido-δ-lactone-type iridoids (21: and 22: ), together with 17 known pentacyclic triterpenoids (3:  - 19: ), were isolated during the phytochemical investigation of a methanol extract of the whole plant of Vaccinium emarginatum. Their structures were determined by detailed analysis of standard spectroscopic data (MS, IR, 1D, and 2D NMR) and comparison with data of known analogs. The isolates were evaluated for their cytotoxicity against the PC-3 and Du145 prostate cancer cell lines (as assessed by an MTT cell proliferation assay), as well as for their anti-inflammatory activity via the inhibition of nitric oxide production in lipopolysaccharide-induced murine macrophage RAW 264.7 cells. Among the isolates, the triterpenoid coumaroyl and feruloyl esters (1, 3: , and 4: ) exhibited strong cytotoxicity against PC-3 prostate cancer cells, with 85.6 - 90.2% inhibition at 10.0 µg/mL. The pomolic acid coumaroyl and feruloyl esters (1: and 3: ) also showed moderate anti-inflammatory activity against nitric oxide production in lipopolysaccharide-induced RAW 264.7 cells, with 59.2 (± 1.0) and 47.1% (± 0.2) inhibition at 12.5 µg/mL, respectively.

New flavonoids, emarginin A-C from Vaccinium emarginatum Hayata.

Phytochemical investigation of methanolic extract of the whole plants of Vaccinium emarginatum allowed for the characterization of one epicatechin derivative (1) that was isolated from a natural source for the first time and three new flavonoids, emarginin A (2), emarginin B (3), and emarginin C (4), together with 11 known compounds (5-15). The structures of compounds 1-4 were elucidated by combination of spectroscopic analysis (MS, IR, and NMR) and by comparison with that of literature analogues. Compounds 1-8 and 11-15 were evaluated for their preliminary in vitro anti-proliferative activity against Du145 and PC-3 prostate cancer cell lines. Among them, compound 15 exhibited most potent cytotoxicity against Du145 and PC-3 cells, with IC50 values of 8.46 and 10.98 µM, respectively. Furthermore, compounds 1-7 were assessed for their anti-inflammatory potential against lipopolysaccharide (LPS)-induced nitric oxide (NO) production in RAW 264.7 cells. Compound 4 exhibited moderate anti-inflammatory activity, with an IC50 value of 27.99 µM.

Chinese Herbal Medicine Ganoderma tsugae Displays Potential Anti-Cancer Efficacy on Metastatic Prostate Cancer Cells.

Resistance to the current therapies is the main clinical challenge in the treatment of lethal metastatic prostate cancer (mPCa). Developing novel therapeutic approaches with effective regimes and minimal side effects for this fatal disease remain a priority in prostate cancer study. In the present study, we demonstrated that a traditional Chinese medicine, quality-assured Ganoderma tsugae ethanol extract (GTEE), significantly suppressed cell growth and metastatic capability and caused cell cycle arrest through decreasing expression of cyclins in mPCa cells, PC-3 and DU145 cells. GTEE also induced caspase-dependent apoptosis in mPCa cells. We further showed the potent therapeutic efficacy of GTEE by inhibiting subcutaneous PC-3 tumor growth in a xenograft model. The in vitro and in vivo efficacies on mPCa cells were due to blockade of the PI3K/Akt and MAPK/ERK signaling pathways associated with cancer cell growth, survival and apoptosis. These preclinical data provide the molecular basis for a new potential therapeutic approach toward the treatment of lethal prostate cancer progression.

Ganoderma tsugae induced ROS-independent apoptosis and cytoprotective autophagy in human chronic myeloid leukemia cells.

The medicinal fungus Ganoderma, known in Chinese as Lingzhi or Reishi, traditionally has various medicinal uses and has been employed in cancer treatment in Asia for centuries. This study used ethanol-extracted Ganoderma tsugae (GT) and examined its antitumor activities on human chronic myeloid leukemia cells as well as its molecular mechanism of action. Treatment with GT (200-400 µg/mL) significantly reduced cell viability and caused G2/M arrest in K562 cells. In addition, GT induced mitochondrial and death receptor mediated apoptosis, correlated with DNA fragmentation, followed by cytochrome c release, caspase-3/8/9 activation, PARP cleavage, Fas activation, Bid cleavage, and Bax/Bcl-2 dysregulation. Cytoprotective autophagy was found to be induced by GT, as was revealed by increased LC3-II accumulation, Beclin-1/Bcl-2 dysregulation, acidic vesicular organelle formation, and p62/SQSTM1 activation. Notably, pretreatment of cells with the autophagy inhibitors 3-MA and CQ enhanced GT-induced apoptosis. Interestingly, reactive oxygen species production in cells was not triggered by GT administration; equally, the antioxidant N-acetylcysteine was found to be incapable of preventing apoptosis and autophagy induced by GT treatment. Finally, this study discovered that cytoprotective autophagy induced by GT was associated with EGFR and PI3K/AKT/mTOR signaling cascade suppression. In summary, GT demonstrated antitumor activity against human chronic myeloid leukemia.

Drynaria fortunei Promoted Angiogenesis Associated With Modified MMP-2/TIMP-2 Balance and Activation of VEGF Ligand/Receptors Expression.

Background and Purpose: Drynaria fortunei J. Sm (D. fortunei), known as Gu-Sui-Bu, is used in traditional Chinese medicine to treat common injuries, including bone fractures and bruising. The specific functional mechanisms of the angiogenic and endothelial cell migration properties of D. fortunei are currently unclear. Thus, the purpose of this study is to validate the potential angiogenic and cellular migration properties and related mechanisms by D. fortunei both in vivo and in vitro. Experimental Approach: The present study investigates, both in vivo and in vitro, the wound healing effects of D. fortunei as associated with angiogenesis, specifically by the modulation of matrix metalloproteinases (MMPs) and upregulation of vascular endothelial growth factor (VEGF) ligand/receptors. In order to determine the potential angiogenic effects of D. fortunei, in vivo neovascularization of chick chorioallantoic membranes (CAMs) assay, and directed in vivo angiogenesis assay (DIVVA) were performed, while in vitro scratch wound healing, migration, and matrix-induced tube formation assays were performed by using human umbilical vascular endothelial cells (HUVECs). Furthermore, we used qPCR to analyze the gene expressions and Western blot to observe protein expressions of MMP-2, MMP-14, TIMP-2, RECK, and VEGF/VEGFRs. Results: This study identified five major compounds from the water extract of D. fortunei: protocatechuic acid, caffeic acid 4-O-ß-D-glucopyranoside, 5,7-dihydroxychromone-7-O-rutinoside, neoeriocitrin, and naringin. D. fortunei was confirmed to activate in vivo angiogenesis by CAM and DIVVA assays. D. fortunei further exhibited in vitro angiogenic effects associated with cell migration, as demonstrated by the tube formation assay, transwell migration assay, and scratch wound healing assay. The extracellular MMP-2 activity was found to be dose-dependently augmented both in vitro and in vivo by D. fortunei. The mRNA and protein expressions of MMP-2, and MMP-14 were increased; while the tissue inhibitor metalloproteinase-2 (TIMP-2), and reversion-inducing cysteine-rich protein with kazal motifs (RECK) were both decreased. Furthermore, D. fortunei activated the gene and protein expressions of VEGF-A, -B, and VEGFR-2, -3. Conclusion: D. fortunei increased MMP-2 activity, thereby stimulating angiogenesis and cell migration, both in vivo and in vitro, as a result of MMP-2 and TIMP-2 balance modulation and the activation of VEGF/VEGFRs expression.

The characteristics and prescription patterns of Chinese herbal medicine in clinical practice for the treatment of anemia.

OBJECTIVE: Chinese herbal medicine (CHM) is frequently applied to patients to improve the symptoms and signs associated with anemia. The aim of this study is to use the claims data from the National Health Insurance Research Database (NHIRD) in Taiwan to analyze CHM prescription patterns and to identify the frequency and combinations of CHM commonly used to treat anemia. MATERIALS AND METHODS: A total of 41,028 patients were diagnosed with anemia in Taiwan within the defined study period. After randomly equal matching for age and sex, data from 7682 patients characterized as CHM users and non-users were analyzed. Network analyses of the 30 most frequently applied herbs and formulas were used to indicate CHM combinations in patients with anemia. RESULTS: Those patients with anemia who were older, office workers, and lived in central areas of Taiwan had higher tendencies toward CHM usage. Based on considerations of comorbidities, anemia patients associated with chronic kidney diseases, diabetes mellitus, and hypertensive diseases preferred Western medical management and demonstrated a lesser likelihood of combining treatment with CHM; by contrast, those with coronary artery disease demonstrated a higher tendency for CHM use. Notably, Astragalus membranaceus (AM) and Gui-Pi-Tang (GPT) were the most commonly prescribed CHM single herb and formula, respectively. The core prescription pattern consisted of AM, Salvia miltiorrhiza (SM), Angelica sinensis (AS), GPT, and Si-Wu-Tang (SWT), as indicated by the associations and frequency of CHM utilization by traditional Chinese medicine (TCM) physicians. CONCLUSION: This study demonstrates that CHM may be applied as an integral element of treatment for patients with anemia. It also provides insight regarding individual therapy and common clinical practices of TCM physicians in the treatment of anemia. Further research is required to explore potential interactions and possible mechanisms at play with CHM management of anemia.

Proteomic profiling of Ganoderma tsugae ethanol extract-induced adipogenesis displaying browning features.

Ganoderma is classified as a top grade traditional Chinese medicine for promoting human health by regulating 'vital energy'. Its potency towards metabolism and energy homeostasis, particularly, metabolic adaptations of adipocytes, needs to be re-evaluated through an evidence-based study. Here, the triterpenoid-rich Ganoderma tsugae ethanol extract (GTEE) was found to contribute towards adipogenesis accompanied with elevated intracellular lipid metabolic flux. Additionally, proteomic profiling revealed GTEE-upregulated mitochondrial remodeling and chemical energy redox modifications, which display UCP1-positive browning fat-selective features and a NADH-mediated adaptive mechanism. GTEE-treated mice with diet-induced obesity also resulted in the amelioration of white adipocyte hypertrophy and the appearance of UCP1-positive browning adipocytes. Our novel findings unravel that GTEE could promote intracellular metabolic flexibility and plasticity followed by the induction of adipocyte browning.

Characterization of Secondary Metabolites from Purple Ipomoea batatas Leaves and Their Effects on Glucose Uptake.

Ipomoea batatas has long been used in folk medicine for the treatment of hyperglycemia or as a food additive for the prevention of type 2 diabetes. However, neither the plant extract nor its active components have been evaluated systematically. In this work four crude extracts, including n-hexane- (IBH), 95% MeOH- (IBM), n-BuOH- (IBB), and H2O-soluble (IBW) fractions, were prepared by fractionation of a methanolic extract of purple I. batatas leaves. Twenty-four pure compounds 1-24 were then isolated by various chromatographic techniques and their structures identified from NMR and MS data. Glucose uptake assays in differentiated 3T3-L1 adipocytes and rat primary hepatocytes, as well as western blot analysis, were carried out to evaluate the antidiabetic activity of this species. The IBH crude fraction, with methyl decanoate (22) as a major and active compound, showed the greatest effect on glucose uptake, most likely via activation of Glut4 and regulation of the PI3K/AKT pathway. Quercetin 3-O-ß-d-sophoroside (1), quercetin (3), benzyl ß-d-glucoside (10), 4-hydroxy-3-methoxybenzaldehyde (12), and methyl decanoate (22) could be important components contributing to the antidiabetic effects. We conclude that purple I. batatas leaves have potential as an antidiabetic plant source and the active constituents 1, 3, 10, 12, and 22 are promising lead candidates for future investigation.

Inhibitory Effects of Purple Sweet Potato Leaf Extract on the Proliferation and Lipogenesis of the 3T3-L1 Preadipocytes.

Purple sweet potato leaves (PSPLs) are healthy vegetable that is rich in anti-oxidants. A solution of boiling water extract of PSPL (PSPLE) is believed to be able to prevent obesity and metabolic syndrome in the countryside of Taiwan, but its efficacy has not yet been verified. The purpose of this study was to investigate the possible anti-adipogenesis effect of PSPLE in vitro. PSPLE was used to treat the 3T3-L1 cells, and the effects on cell proliferation and adipogenesis were investigated. The results showed that PSPLE caused a dose-dependent decrease in the cell proliferation of 3T3-L1 preadipocytes, but did not alter the cell viability. In addition, PSPLE induced ERK inactivation in the 3T3-L1 preadipocytes. Furthermore, pre-treatment of confluent 3T3-L1 cells with PSPLE led to reduced lipid accumulation in differentiated 3T3-L1 cells. The inhibition of lipogenesis could result from the PSPLE-induced down-regulation of the expression of the C/EBPα and SREBP-1 transcription factors during 3T3-L1 adipocyte differentiation. These results suggest that PSPLE not only inhibits cell proliferation at an early stage but also inhibits adipogenesis at a later stage of the differentiation program.

Purple Sweet Potato Leaf Extract Induces Apoptosis and Reduces Inflammatory Adipokine Expression in 3T3-L1 Differentiated Adipocytes.

Background. Purple sweet potato leaves (PSPL) are widely grown and are considered a healthy vegetable in Taiwan. PSPL contain a high content of flavonoids, and the boiling water-extracted PSPL (PSPLE) is believed to prevent metabolic syndrome. However, its efficacy has not yet been verified. Therefore, we investigated the effect of PSPLE on adipocytes. Methods. The differentiated 3T3-L1 cells used in this study were derived from preadipocytes that were differentiated into adipocytes using an adipogenic agent (insulin, dexamethasone, and 3-isobutyl-1-methylxanthine); approximately 90% of the cells were differentiated using this method. Results. Treating the differentiated 3T3-L1 cells with PSPLE caused a dose-dependent decrease in the number of adipocytes rather than preadipocytes. In addition, treatment with PSPLE resulted in apoptosis of the differentiated 3T3-L1 cells as determined by DAPI analysis and flow cytometry. PSPLE also increased the expression of cleaved caspase-3 and poly ADP-ribose polymerase (PARP). Furthermore, PSPLE induced downregulation of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) gene expression in the differentiated 3T3-L1 cells. Conclusions. These results suggest that PSPLE not only induced apoptosis but also downregulated inflammation-associated genes in the differentiated 3T3-L1 cells.

Ganoderma tsugae Extract Inhibits Growth of HER2-Overexpressing Cancer Cells via Modulation of HER2/PI3K/Akt Signaling Pathway.

Ganoderma, also known as Lingzhi or Reishi, has been used for medicinal purposes in Asian countries for centuries. It is a medicinal fungus with a variety of biological properties including immunomodulatory and antitumor activities. In this study, we investigated the molecular mechanisms by which Ganoderma tsugae (GT), one of the most common species of Ganoderma, inhibits the proliferation of HER2-overexpressing cancer cells. Here, we show that a quality assured extract of GT (GTE) inhibited the growth of HER2-overexpressing cancer cells in vitro and in vivo and enhanced the growth-inhibitory effect of antitumor drugs (e.g., taxol and cisplatin) in these cells. We also demonstrate that GTE induced cell cycle arrest by interfering with the HER2/PI3K/Akt signaling pathway. Furthermore, GTE curtailed the expression of the HER2 protein by modulating the transcriptional activity of the HER2 gene and the stability/degradation of the HER2 protein. In conclusion, this study suggests that GTE may be a useful adjuvant therapeutic agent in the treatment of cancer cells that highly express HER2.

Ganoderma tsugae Induces S Phase Arrest and Apoptosis in Doxorubicin-Resistant Lung Adenocarcinoma H23/0.3 Cells via Modulation of the PI3K/Akt Signaling Pathway.

Ganoderma tsugae (GT) is a traditional Chinese medicine that exhibits significant antitumor activities against many types of cancer. This study investigated the molecular mechanism by which GT suppresses the growth of doxorubicin-resistant lung adenocarcinoma H23/0.3 cells. Our results reveal that GT inhibits the viability of H23/0.3 cells in vitro and in vivo and sensitizes the growth suppression effect of doxorubicin on H23/0.3 cells. The data also show that GT induces S phase arrest by interfering with the protein expression of cyclin A, cyclin E, CDK2, and CDC25A. Furthermore, GT induces cellular apoptosis via induction of a mitochondria/caspase pathway. In addition, we also demonstrate that the suppression of cell proliferation by GT is through down-regulation of the PI3K/Akt signaling pathway. In conclusion, this study suggests that GT may be a useful adjuvant therapeutic agent in the treatment of lung cancer.

Rhein induces apoptosis in human breast cancer cells.

Human breast cancers cells overexpressing HER2/neu are more aggressive tumors with poor prognosis, and resistance to chemotherapy. This study investigates antiproliferation effects of anthraquinone derivatives of rhubarb root on human breast cancer cells. Of 7 anthraquinone derivatives, only rhein showed antiproliferative and apoptotic effects on both HER2-overexpressing MCF-7 (MCF-7/HER2) and control vector MCF-7 (MCF-7/VEC) cells. Rhein induced dose- and time-dependent manners increase in caspase-9-mediated apoptosis correlating with activation of ROS-mediated activation of NF-κB- and p53-signaling pathways in both cell types. Therefore, this study highlighted rhein as processing anti-proliferative activity against HER2 overexpression or HER2-basal expression in breast cancer cells and playing important roles in apoptotic induction of human breast cancer cells.

Hyperbaric oxygen upregulates cochlear constitutive nitric oxide synthase.

BACKGROUND: Hyperbaric oxygen therapy (HBOT) is a known adjuvant for treating ischemia-related inner ear diseases. Controversies still exist in the role of HBOT in cochlear diseases. Few studies to date have investigated the cellular changes that occur in inner ears after HBOT. Nitric oxide, which is synthesized by nitric oxide synthase (NOS), is an important signaling molecule in cochlear physiology and pathology. Here we investigated the effects of hyperbaric oxygen on eardrum morphology, cochlear function and expression of NOS isoforms in cochlear substructures after repetitive HBOT in guinea pigs. RESULTS: Minor changes in the eardrum were observed after repetitive HBOT, which did not result in a significant hearing threshold shift by tone burst auditory brainstem responses. A differential effect of HBOT on the expression of NOS isoforms was identified. Upregulation of constitutive NOS (nNOS and eNOS) was found in the substructures of the cochlea after HBOT, but inducible NOS was not found in normal or HBOT animals, as shown by immunohistochemistry. There was no obvious DNA fragmentation present in this HBOT animal model. CONCLUSIONS: The present evidence indicates that the customary HBOT protocol may increase constitutive NOS expression but such upregulation did not cause cell death in the treated cochlea. The cochlear morphology and auditory function are consequently not changed through the protocol.

Ganoderma tsugae extract inhibits expression of epidermal growth factor receptor and angiogenesis in human epidermoid carcinoma cells: In vitro and in vivo.

We examined the anti-angiogenic effects of Ganoderma tsugae methanol extract (GTME) on human epidermoid carcinoma A-431 cells. Our data indicate that GTME inhibits the expression of epidermal growth factor receptor (EGFR) and vascular endothelial growth factor (VEGF) in vitro and in vivo, and also inhibits the capillary tube formation of human umbilical vein endothelial cells (HUVECs). We also show that the suppression of VEGF expression by GTME can be restored by treatment with EGF. These results suggest that GTME inhibits VEGF expression via the suppression of EGFR expression, resulting in the downregulation of VEGF secretion from epidermoid carcinoma A-431 cells. These findings reveal a novel role for G. tsugae in inhibiting EGFR and VEGF expression, which are important for tumor angiogenesis and growth. Thus, GTME may provide a potential therapeutic approach for anti-tumor treatment.

Gypenosides induced G0/G1 arrest via CHk2 and apoptosis through endoplasmic reticulum stress and mitochondria-dependent pathways in human tongue cancer SCC-4 cells.

Gypenosides (Gyp), a component of Gynostemma pentaphyllum Makino, was selected for examining the effects on the cell viability, cell cycle and induction of apoptosis in human tongue cancer SCC-4 cells. Gyp induced cytotoxicity (decreased the percentage of viable cells) in SCC-4 cells appeared to be associated with induction of cell cycle arrest (G0/G1 arrest), apoptotic cell death based on Gyp induced morphological changes and DNA fragmentation and increased the sub-G1 group in examined SCC-4 cells. The production of reactive oxygen species and Ca(2+) and the depolarization of mitochondrial membrane potential were observed, dose- and time-dependently, after treatment of SCC-4 cells with various concentrations of Gyp. Gyp inhibited the levels of the anti-apoptotic proteins Bcl-2 and Bcl-xl, but promoted the levels of the pro-apoptotic protein Bax. Western blotting showed the releases of cytochrome c and Endo G and both were also confirmed by confocal laser microscopic systems. The GADD153 moved to nuclei (nuclear translocation). In conclusion, Gyp induced ER stress and production of reactive oxygen species and Ca(2+), change the ratio of Bcl-2 and Bax, followed by the dysfunction of mitochondria, caused cytochrome c release, activation of caspase-3 before leading to apoptosis. These results provide information towards an understanding of the mechanisms by which Gyp induces cell cycle arrest and apoptosis in human tongue cancer cells.

Ganoderma tsugae extracts inhibit colorectal cancer cell growth via G(2)/M cell cycle arrest.

ETHNOPHARMACOLOGICAL RELEVANCE: Ganoderma, known as Lingzhi or Reishi, has been traditionally administered throughout Asia for centuries as a cancer treatment and for other medicinal purposes. AIM OF THE STUDY: To investigate the inhibitory activity and explore the molecular mechanisms of anti-tumor effect on colorectal cancer cells in vitro and in vivo as well as to test the side effects of Ganoderma tsugae. MATERIALS AND METHODS: Methanol fraction was obtained from dried fruiting bodies of Ganoderma. TLC and HPLC were performed to differentiate and confirm the identification of different species as well as to quantify the bioactive molecules in methanol extracts of Ganoderma species. MTT and Trypan blue exclusion assay as well as tumorigenesis study were used to assess the anti-tumor effect in vitro and in vivo. Using flow cytometry and Western Blots, we examined further the molecular mechanisms of anti-tumor effect. Finally, biochemical and hematological profiles and pathological examinations were used to evaluate the safety. RESULTS: The Ganoderma tsugae extracts inhibit colorectal cancer cell proliferation caused by accumulating cells in G(2)/M phase, and it may be through downregulation of cyclin A and B1 and upregulation of p21 and p27. Tumorigenesis study in nude mice revealed the extracts caused tumor shrinkage. Additionally, safety assay showed Ganoderma tsugae extracts caused no significant side effects in an animal model. CONCLUSIONS: This study provides molecular evidence that Ganoderma tsugae extracts exert anti-tumor effects both in vitro and in vivo on colorectal adenocarcinoma cells by inducing G(2)/M cell cycle arrest. More importantly, no significant physiological changes resulting from treatment with Ganoderma tsugae extracts were observed in the animal model. Therefore, these data provide new insights into the possible therapeutic use of Ganoderma tsugae for treating colorectal cancer.

Black tea polyphenol theaflavins inhibit aromatase activity and attenuate tamoxifen resistance in HER2/neu-transfected human breast cancer cells through tyrosine kinase suppression.

The aromatase enzyme, which converts androstenedione to oestrone, regulates the availability of oestrogen to support the growth of hormone-dependent breast tumours. In this study, we investigated the inhibitory effects of black tea polyphenols on aromatase activities. We found that black tea polyphenols, TF-1, TF-2 and TF-3, significantly inhibited rat ovarian and human placental aromatase activities. In addition, using an in vivo model, these black tea polyphenols also inhibited the proliferation induced by 100 nM dehydroepiandrosterone (DHEA) in MCF-7 cells. Transfection of HER2/neu in MCF-7 breast cancer cells appeared to be associated with an increased resistance of the cells to hormonal therapy. Interestingly, unlike the selective oestrogen receptor modulator (SERM) tamoxifen, black tea polyphenols had antiproliferation effects in breast cancer cells with hormonal resistance. The inhibitory effect of black tea polyphenols on hormone-resistant breast cancer cells suppressed the basal receptor tyrosine phosphorylation in HER2/neu-overexpressing MCF-7 cells. These findings suggest the use of black tea polyphenols may be beneficial in the chemoprevention of hormone-dependent breast tumours and represent a possible remedy to overcome hormonal resistance of hormone-independent breast tumours.