2-Hydroxychalcone and Xanthohumol Inhibit Invasion of Triple Negative Breast Cancer Cells

18th Tuesday, 2013  |   Breast Cancer, Herb or Compound  |  no comments

Chalcone is an aromatic ketone and an enone that forms the central core for a variety of important biological compounds, which are known collectively as chalcones or chalconoids. Benzylideneacetophenone is the parent member of the chalcone series. The alternative name given to chalcone are phenyl styryl ketone, benzalacetophenone, ?-phenylacrylophenone, ?-oxo-?,?-diphenyl-?-propylene and ?-phenyl-?-benzoylethylene.


2-Hydroxychalcone and Xanthohumol Inhibit Invasion of Triple Negative Breast Cancer Cells

Kim SY, Lee IS, Moon A. Chem Biol Interact. 2013 May 25;203(3):565-72. doi: 10.1016/j.cbi.2013.03.012. Epub 2013 Apr 3.
Breast cancer is estimated as one of the most common causes of cancer death among women. In particular, triple negative breast cancers (TNBCs), which do not express the genes for estrogen/progesterone receptors (ER/PR) and human epidermal growth factor receptor 2 (HER2), have been associated with poor prognosis and metastasis.
Chalcones, the biosynthetic precursors of flavonoids present in edible plants, exert cytotoxic and chemopreventive activities. Although mounting evidence suggests the anticancer properties of chalcones, limited information is available regarding the inhibitory effects of chalcones on the aggressiveness of breast cancer cells. The present study aimed to investigate the effects of chalcone and its derivatives on the growth and the invasiveness of TNBC cells.
Here, we showed that treatment with chalcone, 2-hydroxychalcone, and xanthohumol for 24h inhibited the growth of MDA-MB-231cells with IC50 values of 18.1, 4.6, and 6.7?M, respectively. Similarly, Chalcone, 2-hydroxychalcone, and xanthohumol also exerted cytotoxicity in another TNBC cell line, Hs578T. Neohesperidin dihydrochalcone, 4-methoxychalcone, and hesperidin methylchalcone did not show the cytotoxicity on the MDA-MB-231cells. Xanthohumol and 2-hydroxychalcone induced apoptosis by Bcl-2 downregulation. Importantly, 2-hydroxychalcone and xanthohumol exerted more potent inhibitory effects on the proliferation, MMP-9 expression and invasive phenotype of MDA-MB-231 than chalcone.
These results suggest a potential application of these chalcones as anticancer agents that can alleviate malignant progression of TNBC.

Remarkable Anti-Breast Cancer Activity of Ferrocene Tagged Multi-Functionalized 1,4-Dihydropyrimidines.

Jadhav J, Juvekar A, Kurane R, et al. Eur J Med Chem. 2013 Apr 28;65C:232-239. doi: 10.1016/j.ejmech.2013.04.021.
A novel series of ferrocene tagged multi-functionalized 1,4-dihydropyrimidines is synthesized by base catalyzed cyclocondensation between ferrocenyl chalcones and amidines. The structures of synthesized compounds were established on the basis of 1H NMR, 13C NMR, FTIR spectroscopy as well as by mass spectrometry.
The compounds were evaluated for in vitro anticancer activity. The most active compounds from the series displayed GI50 value equal to doxorubicin against the strain of human breast cancer cell line MDA-MB-435.

The Molecular Mechanisms of Traditional Chinese Medicine ZHENG Syndromes on Pancreatic Tumor Growth.

18th Tuesday, 2013  |   Others, Pancreatic Cancer  |  no comments

Dai HY, Wang P, Feng LY, Liu LM, et al. Integr Cancer Ther. 2010 Sep;9(3):291-7. doi: 10.1177/1534735410373922. Epub 2010 Aug 11.


Traditional Chinese medicine (TCM) syndromes (ZHENG in Chinese) are the abstraction from the comprehensive analysis of clinical information gained by the four main diagnostic TCM methods: observation, listening, questioning, and pulse analyses. Proper TCM diagnosis is the most important principle to guide the prescribing of Chinese herbs.
This study evaluated the specific effect of TCM ZHENG on tumor growth and to examine the molecular mechanisms underlying ZHENG and tumor growth.
The authors established subcutaneous tumor models of pancreatic cancer ZHENG syndromes of Damp heat (Shi-Re) and Spleen deficiency (Pi-Xu). Tissue samples of the subcutaneous transplanted tumors from each model were studied versus control tumors. CCR5 and CXCR4 proteins in these tissues were assayed by immunohistochemical staining. The expression of CCR5/CCL5/CCL4/CCL3 and CXCR4/SDF-1 mRNA was investigated by reverse transcriptase-polymerase chain reaction (RT-PCR). SDF-1, CCL4, CCL5, and CCL3, which are ligands of CXCR4 and CCR5, were examined by ELISA.
The study found that tumor models with different ZHENG were successfully established in each group; the tumor growth of Shi-Re group was slower than that of the control group. It was found that there was a significant difference in CCR5 mRNA expression levels among the Pi-Xu, Shi-Re, and control groups. The results of immunohistochemistry staining revealed that the positive rate of CCR5 protein in Shi-Re group, Pi-Xu group, and control group was 25.00%, 53.33%, 83.33%, respectively. The Shi-Re group expressed the lowest levels of CCL5 and CCL4.
The results of the study suggest that the existence of TCM ZHENG may influence the tumor growth in pancreatic cancer, which might be mediated by the expression of CCR5/CCL5/CCL4. This finding may lead to the development of TCM ZHENG as a prognostic indicator in pancreatic tumor growth.

Therapeutic Effects of Saireito (Chai-Ling-Tang), a Traditional Japanese Herbal Medicine, on Lymphedema Caused by Radiotherapy: A Case Series Study

12th Wednesday, 2013  |   Herb or Compound  |  no comments


Nagai A, et al. Evidence-Based Complementary and Alternative Medicine. Volume 2013 (2013) http://dx.doi.org/10.1155/2013/241629

Chai Hu

Despite the development of radiotherapy machines and technologies, a proportion of patients suffer from radiation-induced lymphedema. Saireito cialisonline-genericrxed.com (SRT) is a traditional Japanese herbal medicine that has been used for treating edema and inflammation in conditions such as nephritic disease. This study investigated the effect of SRT on lymphedema caused by radiotherapy. Four patients were treated with SRT at a dose of 9?g/day. The severity of lymphedema was evaluated using the Common Terminology Criteria for Adverse Events version 4 and Numerical Rating Scale before and after SRT treatment.

After the treatment with SRT, 2 of 4 patients (50%) showed apparent improvement in lymphedema. One of the cases had difficulty in wearing the custom-made thermoplastic cast, but after SRT administration, he could wear the mask easily. One case decided to stop taking SRT 3 days after initiation because cough and fever appeared.

In conclusion, it is important to control the side effects of radiotherapy, which leads to improved tumor control rates. Prospective randomized studies are necessary to confirm the findings of this case series study.

Saireito is composed of 12 crude drugs in fixed proportions: 7.0?g of Bupleurum root, 5.0?g of Pinellia tuber, 5.0?g of Alisma rhizome, 3.0?g of Scutellaria root, 3.0?g of ginseng, 3.0?g of Poria sclerotium, 3.0?g of Polypoms sclerotium, 3.0?g of Astractylodes lancea rhizome, 3.0?g of jujube, 2.0?g of Glycyrrhiza, 2.0?g of cinnamon bark, and 1.0?g of ginger. Saikosaponin, which is derived from the medicinal plant Bupleurum root, exhibits a variety of pharmacological and immune-modulatory activities including anti-inflammatory responses.

The Role of IL-17-producing Foxp3+ CD4+ T Cells in Inflammatory Bowel Disease and Colon Cancer

12th Wednesday, 2013  |   Inflammation, Others  |  no comments

Source: Li L, Boussiotis VA. Clinical Immunology. 15 May 2013 http://dx.doi.org/10.1016/j.clim.2013.05.003 1-s2.0-S152166161300123X-gr1 Figure 1. Induction of TReg cell mediated gut immune tolerance.In the steady state, gut immune tolerance is induced and maintained by a variety of mechanisms, which regulate the differentiation and activation of TReg cells. Some commensal bacteria can induce the differentiation of CD4+ T cells into TReg cells in a TLRs dependent manner. Clostridium spp. can induce generation of IL-10 producing TReg cells via epithelial cell-derived TGF-?, whereas Bacteroides fraglilis can induce IL-10 producing TReg cells via polysaccharide A (PSA). CD103+DC can also induce TReg cells through their ability to produce retinoic acid and TGF-?. TReg cells act on macrophage and myeloid cells to inhibit their ability to produce colitogenic cytokines including IL-12p40, Il-6 and IL-23, which are required for the differentiation of CD4+ T cells into Th1 and Th17 cells. Both Th1 and Th17 cells are associated with initiation and progression of IBD and colon cancer. TReg cells suppress inflammatory responses mainly through production of anti-inflammatory cytokines TGF-? and more importantly IL-10. The intestinal epithelium and underlying lamina propria contain T cells that play important roles in maintaining colonic homeostasis. These T cells mediate substantial and specific regulation to ensure that pathogenic microorganisms are eliminated while commensal bacteria are tolerated. There is considerable evidence supporting the notion that the altered ratio between Foxp3+CD4+ T regulatory cells and T effector cells in the colonic microenvironment might contribute to the initiation and progression of inflammation and eventually development of colon cancer. Recent findings on the heterogeneity and plasticity of T regulatory cells, such cialis 20mg buy as the identification of IL-17+Foxp3+CD4+ and the ROR?t+Foxp3+CD4+ subsets, in patients with colorectal inflammation and cancer have provided a new twist in our understanding of the pathogenesis of colonic diseases. Phenotypic and functional properties of IL-17-producing Foxp3+CD4+ T cells as well as the significant implications of these cells in the initiation and progression of colorectal diseases are discussed in this review. Increased CYP4B1 mRNA is Associated with the Inhibition of Dextran Sulfate Sodium–Induced Colitis by Caffeic Acid in Mice Ye Z, Liu Z, Henderson A, et al. Exp Biol Med (Maywood) June 2009 vol. 234 no. 6 605-616 doi: 10.3181/0901-RM-1 Susceptibility to inflammatory bowel diseases depends upon interactions between the genetics of the individual and induction of chronic mucosal inflammation. We hypothesized that administration of dietary phenolics, caffeic acid and rutin, would suppress upregulation of inflammatory markers and intestinal damage in a mouse model of colitis. Colitis was induced in C3H/ HeOuJ mice (8 weeks old, 6 male/6 female per treatment) with 1.25% dextran sulfate sodium (DSS) for 6 d in their drinking water. Rutin (1.0 mmol (524 mg)/kg in diet), caffeic acid (1.0 mmol (179 mg)/kg in diet), and hypoxoside extract (15 mg/d, an anticolitic phenolic control) were fed to the mice for 7 d before and during DSS treatment, as well as without DSS treatment. Body weight loss was prevented by rutin and caffeic acid during DSS treatment. Colon lengths in mice fed caffeic acid and hypoxoside during DSS treatment were similar to DSS-negative control. Food intake was improved and myeloperoxidase (MPO) was decreased with each phenolic treatment in DSS-treated mice compared with DSS treatment alone. Colonic mRNA expression of IL-17 and iNOS were inhibited when IL-4 was increased by each phenolic treatment combined with DSS, whereas CYP4B1 mRNA was increased only by caffeic acid in DSS-treated mice, compared with DSS treatment alone. Colonic and cecal histopathology scores of DSS-treated mice were significantly more severe (P < 0.01) than in mice fed caffeic acid before and during DSS treatment, based on mucosal height, necrosis, edema, erosion, and inflammatory cell infiltration. Although both rutin and caffeic acid suppressed the expression of selected inflammatory markers, only caffeic acid protected against DSS-induced colitis, in association with normalization of CYP4B1 expression. The inhibition of DSS-induced colitic pathology by caffeic acid was mediated by mechanisms in addition to anti-inflammatory effects that deserve further study.

Systems Approaches to Molecular Cancer Diagnostics

11th Tuesday, 2013  |   Others  |  no comments


Ma S, Funf CC, Price ND, et al. Discovery Medicine. Dec 26, 2010 http://www.discoverymedicine.com/Shuyi-Ma/2010/12/26/systems-approaches-to-molecular-cancer-diagnostics/

The search for improved molecular cancer diagnostics is a challenge for which systems approaches show great promise. As is becoming increasingly clear, cancer is a perpetually-evolving, highly multi-factorial disease. With next generation sequencing providing an ever-increasing amount of high-throughput data, the need for analytical tools that can provide meaningful context is critical.

Systems approaches have demonstrated an ability to separate meaningful signal from noise that arises from population heterogeneity, heterogeneity within and across tumors, and multiple sources of technical variation when sufficient sample sizes are obtained and standardized measurement technologies are used.

The ability to develop clinically useful molecular cancer diagnostics will be predicated on advancements on two major fronts:

1) more comprehensive and accurate measurements of multiple endpoints, and

2) more sophisticated analytical tools that synthesize high-throughput data into meaningful reflections of cellular states.

To this end, systems approaches that have integrated transcriptomic data onto biomolecular networks have shown promise in their ability to classify tumor subtypes, predict clinical progression, and inform treatment options. Ultimately, the success of systems approaches will be measured by their ability to develop molecular cancer diagnostics through distilling complex, systems-wide information into actionable information in the clinic.