genetics

Gene expression profiling reveals effects of Cimicifuga racemosa (L.) NUTT. (black cohosh) on the estrogen receptor positive human breast cancer cell line MCF-7.: BMC Pharmacol. 2007 Sep 20; 7(1): 11 Gaube F, Wolfl S, Pusch L, Kroll TC, Hamburger M

ABSTRACT: BACKGROUND: Extracts from the rhizome of Cimicifuga racemosa (black cohosh) are increasingly popular as herbal alternative to hormone replacement therapy (HRT) for the alleviation of postmenopausal disorders. However, the molecular mode of action and the active principles are presently not clear. Previously published data have been largely contradictory. We, therefore, investigated the effects of a lipophilic Cimicifuga rhizome extract and cycloartane-type triterpenoids on the estrogen receptor positive human breast cancer cell line MCF-7. RESULTS: Both extract and purified compounds clearly inhibited cellular proliferation. Gene expression profiling with the extract allowed us to identify 431 regulated genes with high significance. The extract induced expression pattern differed from those of 17beta-estradiol or the estrogen receptor antagonist tamoxifen. We observed a significant enrichment of genes in an anti-proliferative and apoptosis-sensitizing manner, as well as an increase of mRNAs coding for gene products involved in several stress response pathways. These functional groups were highly overrepresented among all regulated genes. Also several transcripts coding for oxidoreductases were induced, as for example the cytochrome P450 family members 1A1 and 1B1. In addition, some transcripts associated with antitumor but also tumor-promoting activity were regulated. Real-Time RT-PCR analysis of 13 selected genes was conducted after treatment with purified compounds - the cycloartane-type triterpene glycoside actein and triterpene aglycons - showing similar expression levels compared to the extract. CONCLUSION: No estrogenic but antiproliferative and proapoptotic gene expression was shown for black cohosh in MCF-7 cells at the transcriptional level. The effects may be results of the activation of different pathways. The cycloartane glycosides and - for the first time - their aglycons could be identified as an active principle in black cohosh.

Herbal diterpenoids induce growth arrest and apoptosis in colon cancer cells with increased expression of the nonsteroidal anti-inflammatory drug-activated gene.: Eur J Pharmacol. 2006 Dec 23; Authors: Ko JK, Leung WC, Ho WK, Chiu P

Novel chemotherapeutic agents derived from active phytochemicals could be used as adjuvants and improve the anti-carcinogenicity of standard drug treatments. However, their precise mechanisms of action are sometimes unclear. In this study, the anti-carcinogenic effect of the herbal diterpenoid pseudolaric acid B (PAB) on the growth and apoptosis of colon cancer cells was investigated, and to compare that with the more toxic compound triptolide. PAB induced growth inhibition and apoptosis in HT-29 cells, which were associated with cell cycle arrest at the G(2)/M phase, modulation of cyclin expression and downregulation of the protooncogene c-myc. In addition, PAB also inhibited bcl-x(L) expression, induced cleavage of procaspase-3 and its substrate poly(ADP-ribose) polymerase (PARP), which together caused DNA fragmentation and nuclear chromatin condensation. Concomitantly, the modulation of the growth-related and apoptotic factors by PAB was accompanied by the increased protein and gene expression of the nonsteroidal anti-inflammatory drug-activated gene (NAG-1), which occurred along with cyclooxygenase-2 inhibition. The effects of PAB on PARP cleavage and NAG-1 overexpression were not reversible upon removal of the drug from the culture medium. Similar cytotoxic and pro-apoptotic effects were also attained by treating the HT-29 cells with another diterpenoid triptolide, but its actions on cell cycle progression and on the upstream transcriptional regulation of NAG-1 both took place in a less coherent manner. These findings exemplify the potential of herbal terpenoids, particularly PAB, in modulating colon cancer carcinogenesis through known molecular targets and precise mechanism of action.

Effect of Ganoderma lucidum on human DNA is dose dependent and mediated by hydrogen peroxide.: Redox Rep. 2005;10(3):145-9 Authors: Wachtel-Galor S, Choi SW, Benzie IF

Ganoderma lucidum, an oriental fungus, is widely used for the promotion of health and longevity and is reported to have antioxidant and genoprotective properties. The aim of this study was to investigate the effect of G. lucidum on human lymphocytic DNA ex vivo using the comet assay, and to explore the mechanism of action and the effect of dose. Results showed that G. lucidum has a genoprotective effect at low concentration (0.0001% w/v), but damaged DNA at higher concentrations. The mechanism of damage appeared to be mediated by hydrogen peroxide, which was generated in vitro by G. lucidum, as the effect was ameliorated by the presence of catalase. At concentrations at which no damage was induced, G. lucidum appeared to confer protection against subsequent oxidant challenge to cells. The production of hydrogen peroxide by G. lucidum and its cytotoxic effects should be considered as a factor in future studies. However, the protective effect of G. lucidum at low concentration may explain, in part, some of the reported health benefits of this herb.

The p53 Tumor Suppressor: A Story of Death and Degradation:

Presented by: Karen Vousden, Ph.D., FRS, Beatson Institute for Cancer Research, Glasgow, Scotland

Aired date: 10/21/2003 4:00:00 PM Eastern Time