Composition and mechanism of antitumor effects of <i>Hericium erinaceus</i> mushroom extracts in tumor-bearing mice.
J Agric Food Chem. 2011 Aug 16;
Authors: Kim SP, Kang MY, Kim JH, Nam SH, Friedman M
Abstract We investigated antitumor effects of the following four extracts of freeze-dried <i>Hericium erinaceus</i> mushrooms in Balb/c mice intracutaneously transplanted on the backs with CT-26 colon cancer cells: HWE, hot-water extraction by boiling in water for 3 h; MWE, microwaving in 50% ethanol/water at 60 W for 3 min; ACE and AKE, boiling in 1% HCl or 3% NaOH for 2 h. HWE and MWE with a higher content of ?-glucans, determined by an assay kit, than ACE and MKE were active in all bioassays. GC/MS analyses showed the presence of 40, 27, 16, and 13 compounds, respectively, in the four extracts. Daily intraperitoneal (ip) injections of HWE and MWE for 2 weeks significantly reduced tumor weights by 38% and 41%. Tumor regressions were associated with changes in the following cancer biomarkers compared to phosphate buffer (PBS) treated control mice: 2.7- and 2.4-fold increases in cytolytic activity of splenic natural killer (NK) cells; restored NO production and phagocytosis in peritoneal macrophages to 95-98% of normal levels; ~2-fold increase in released pro-inflammatory cytokines TNF-?, IL-1?, and IL-6 from macrophages; and ~56% and ~60% reductions in the number of blood vessels inside the tumor. The pro-angiogenic factors VEGF, COX-2, and 5-LOX were also significantly reduced in mRNA and protein expression by tumor genes. ELISA of tumor cells confirmed reduced expression of COX-2 and 5-LOX (32% and 31%). Reduced COX-2 and 5-LOX expression down-regulated VEGF expression, resulting in inhibition of neo-angiogenesis inside the tumors. The results indicate that induction of NK activity, activation of macrophages, and inhibition of angiogenesis all contribute to the mechanism of reduction of tumor size.
PMID: 21846141 [PubMed - as supplied by publisher]
Cancer selective metallocenedicarboxylates of the fungal cytotoxin illudin M.
J Med Chem. 2011 Aug 18;
Authors: Schobert R, Seibt S, Mahal K, Ahmad A, Biersack B, Effenberger-Neidnicht K, Padhye S, Sarkar FH, Mueller T
Abstract The diester 2a obtained from 1,1'-ferrocenedicarboxylic acid and the highly and indiscriminately cytotoxic fungal metabolite illudin M (1) displayed antiproliferative activity at submicromolar IC50(72 h) values against a panel of eight cancer cell lines. Compound 2a was about forty times less toxic than 1 to non-malignant human foreskin fibroblasts (HF). The analogous bis(illudinyl M) 1,1'-ruthenocenedicarboxylate (2b) exhibited submicromolar IC50(72 h) values only against MDA-MB-231 and MCF-7/Topo breast carcinoma and HL-60 leukemia cells. Cytotoxicity studies in the presence of inhibitors of c-Jun N-terminal kinase (JNK) or extracellular signal-regulated kinase (ERK) revealed that the high efficacy of 2a, but not that of 2b, against HCT-116 colon cancer cells depends on active JNK/ERK signaling. A new illudin M lactone 5 was of low anticancer activity, but its ruthenocene diester 6b also reached single-digit micromolar IC50(72 h) values in HCT-116, MCF-7, and HL-60 leukemia cells while not affecting HF. Compounds 2a and 6b were tolerated by mice symptom-free at single doses as high as 25 mg/kg body weight which is evidence for them being chemically stable under physiological conditions. Compound 2a displayed a manageable in vivo toxicity profile when given repeatedly in high doses.
PMID: 21848340 [PubMed - as supplied by publisher]
Anti-Angiotensin and Hypoglycemic Treatments Suppress Liver Metastasis of Colon Cancer Cells.
Pathobiology. 2011 Aug 18;78(5):285-290
Authors: Luo Y, Ohmori H, Shimomoto T, Fujii K, Sasahira T, Chihara Y, Kuniyasu H
Abstract The effect of diabetic conditions on liver metastasis was examined using CT26 mouse colon cancer cells. CT26 cells produced angiotensin (A)-I and A-II from angiotensinogen; the production was abrogated by inhibitors of renin and chymase. Renin expression and A-II production increased with an increase in the concentration of glucose in the medium. In a streptozotocin-induced BALB/c mouse diabetes model that was fed a high-calorie diet, the blood sugar level increased and was associated with an increasing size and number of CT26 liver metastases. In this diabetic mouse model, liver metastasis of CT26 cells was suppressed by anti-angiotensin treatment with a chymase inhibitor, a renin inhibitor, and an A-II receptor blocker. Moreover, concurrent hypoglycemic and anti-angiotensin treatments showed a synergistic inhibitory effect on CT26 cell liver metastasis. These results suggest that angiotensin activation ability associated with diabetic conditions enhances liver metastasis of colon cancer. Therefore, treatment with anti-angiotensin and hypoglycemic agents might be relevant for baseline management of colon cancer patients with the diabetic condition for the prevention of liver metastasis. This scheme needs to be examined in a clinical setting.
PMID: 21849810 [PubMed - as supplied by publisher]
Dynamics of bivalent chromatin domains upon drug induced reactivation and resilencing in cancer cells.
Epigenetics. 2011 Sep 1;6(9)
Authors: Mayor R, Muñoz M, Coolen MW, Custodio J, Esteller M, Clark SJ, Peinado MA
Abstract Epigenetic deregulation revealed by altered profiles of DNA methylation and histone modifications is a frequent event in cancer cells and results in abnormal patterns of gene expression. Cancer silenced genes constitute prime therapeutic targets and considerable progress has been made in the epigenetic characterization of the chromatin scenarios associated with their inactivation and drug induced reactivation. Despite these advances, the mechanisms involved in the maintenance or resetting of epigenetic states in both physiological and pharmacological situations are poorly known. To get insights into the dynamics of chromatin regulation upon drug-induced reactivation, we have investigated the epigenetic profiles of two chromosomal regions undergoing long range epigenetic silencing in colon cancer cells in time-course settings after exposure of cells to chromatin reactivating agents. The DNA methylation states and the balance between histone H3K4 methylation and H3K27 methylation marks clearly define groups of genes with alternative responses to therapy. Drug reactivated cancer silenced genes exhibit dominant bivalent chromatin states that overcome the treatment and restore the transcriptional silencing approximately four weeks after drug exposure. The interplay between DNA methylation and bivalent histone marks appears to configure a plastic but stable chromatin scenario that is fully restored in silenced genes after drug withdrawal.
PMID: 21852760 [PubMed - as supplied by publisher]
You can link to this article on your web site using following code:
We're looking for comments that are interesting, substantial or highly amusing. If your comments are excessively self-promotional (use your real name, no keywords please), obnoxious, or even worse, boring, you will be banned from commenting. Your comment must be related to the post. Please do not comment on how great or wonderful the post is. All comments are moderated and, if approved, will display in less than 24 hours.