The same flavonoid reported in the last post, this time extracted from Smilax, inhibiting cervical cancer cell line HeLa.

Kaempferol-7-O-beta-D-glucoside (KG) isolated from Smilax china L. rhizome induces G2/M phase arrest and apoptosis on HeLa cells in a p53-independent manner.:

Cancer Lett. 2008 Jun 18;264(2):229-40

Authors: Xu W, Liu J, Li C, Wu HZ, Liu YW

Kaempferol-7-O-beta-D-glucoside (KG), a flavonoid glycoside, isolated from Smilax china L. rhizome, displayed marked anticancer activity on a panel of established cancer cells, of which, HeLa human cervix carcinoma cells were the most sensitive. Meanwhile, the cytotoxic effects of KG on normal human cells (HEK293 embryonic kidney cells and L-02 embryonic liver cells) were much smaller than on cancer cells. This work studied the molecular mechanisms underlying KG induced growth inhibition in HeLa cells. The results showed that KG induced G2/M phase growth arrest correlated with Cyclin B1 and Cdk1 decrease in a p53-independent manner, and also caused an increase in apoptosis, which was confirmed by characteristic morphological changes, evident DNA fragmentation, increased apoptotic sub-G1 population. Furthermore, inhibition of NF-kappaB nuclear translocation, up-regulation of Bax and down-regulation of Bcl-2, were observed in HeLa cells treated with KG, which indicated that the mitochondrial pathway was involved in the apoptosis signal pathway. In summary, KG displayed a significant anti-tumor effect through cell cycle arrest and apoptotic induction in HeLa cells, which suggested that KG might have therapeutic potential against cervix carcinoma.

PMID: 18343026 [PubMed - indexed for MEDLINE]

Another study demonstrating the the anticancer properties of ginkgo and its constituents - now with pancreatic cancer.

Ginkgo biloba extract kaempferol inhibits cell proliferation and induces apoptosis in pancreatic cancer cells.

J Surg Res. 2008 Jul;148(1):17-23

Authors: Zhang Y, Chen AY, Li M, Chen C, Yao Q

BACKGROUND: Kaempferol is one of the most important constituents in ginkgo flavonoids. Recent studies indicate kaempferol may have antitumor activities. The objective of this study was to determine the effect and mechanisms of kaempferol on pancreatic cancer cell proliferation and apoptosis. MATERIALS AND METHODS: Pancreatic cancer cell lines MIA PaCa-2 and Panc-1 were treated with kaempferol, and the inhibitory effects of kaempferol on pancreatic cancer cell proliferation were examined by direct cell counting, 3H-thymidine incorporation, and MTS assay. Lactate dehydrogenase release from cells was determined as an index of cytotoxicity. Apoptosis was analyzed by terminal deoxynucleotidyl transferase mediated dUTP nick end labeling assay. RESULTS: Upon the treatment with 70 microm kaempferol for 4 days, MIA PaCa-2 cell proliferation was significantly inhibited by 79% and 45.7% as determined by direct cell counting and MTS assay, respectively, compared with control cells (P < 0.05). Similarly, the treatment with kaempferol significantly inhibited Panc-1 cell proliferation. Kaempferol treatment also significantly reduced 3H-thymidine incorporation in both MIA PaCa-2 and Panc-1 cells. Combination treatment of low concentrations of kaempferol and 5-fluorouracil showed an additive effect on the inhibition of MIA PaCa-2 cell proliferation. Furthermore, kaempferol had significantly less cytotoxicity than 5-fluorouracil in normal human pancreatic ductal epithelial cells (P = 0.029). In both MIA PaCa-2 and Panc-1 cells, apoptotic cell population was increased when treated with kaempferol in a concentration-dependent manner. CONCLUSIONS: Ginkgo biloba extract kaempferol effectively inhibits pancreatic cancer cell proliferation and induces cancer cell apoptosis, which may sensitize pancreatic tumor cells to chemotherapy. Kaempferol may have clinical applications as adjuvant therapy in the treatment of pancreatic cancer.

PMID: 18570926 [PubMed - indexed for MEDLINE]

Effects of rhubarb extract on radiation induced lung toxicity via decreasing transforming growth factor-beta-1 and interleukin-6 in lung cancer patients treated with radiotherapy. Yu HM, Liu YF, Cheng YF, Hu LK, Hou M, Lung Cancer. 2008 Feb;59(2):219-26

BACKGROUND: Radiation induced lung toxicity (RILT) is the main adverse effect in the radiation therapy of lung cancer. However, the optimal management of RILT has not been defined. In this paper, we investigated the effects of rhubarb extract on RILT, pulmonary function (PF), transforming growth factor-beta-1 (TGF-beta1), and interleukin-6 (IL-6) in lung cancer patients treated with radiotherapy. PATIENTS AND METHODS: We conducted a randomized, double-blind, placebo-controlled trial. Eighty consecutive patients were randomly enrolled into two groups: trial group and control group. The trial group received three-dimensional conformal radiation therapy (3D-CRT) plus rhubarb (at a dose of 20 mg kg(-1) once a day) for 6 weeks. The control group received 3D-CRT plus a placebo containing starch for 6 weeks. Plasma TGF-beta1 and serum IL-6 were measured in all patients before, every 2 weeks during, and at 6 weeks after the completion of the treatment. RILT and PF were evaluated at 6 weeks and 6 months after the end of the treatment, respectively. The differences of TGF-beta1, IL-6, RILT, and PF between the two groups were analysed. RESULTS: The incidence of RILT in the trial group was significantly lower than that in the control group at 6 weeks and 6 months after treatment (32.4% versus 56.7% at week 6, and 27.0% versus 52.8% at month 6, both P<0.05). The plasma TGF-beta1 levels in the trial group were significantly lower than that in the control group during and after the treatment (P<0.05 or 0.01, respectively). The serum IL-6 levels in the trial group were significantly lower than that in the control group during the treatment (all P<0.01). The forced vital capacity (FVC), forced expiratory volume at 1s (FEV1) at 6 weeks and the diffusion capacity for carbon monoxide (DLCO) at 6 months in the trial group were significantly improved compared to the control group (P<0.05 or 0.01, respectively). CONCLUSIONS: The rhubarb extract significantly attenuated RILT and improved PF, probably by decreasing the level of TGF-beta1 and IL-6. These results may be of value for the prophylaxis of RILT, but the exact mechanisms underlying these prophylactic effects remain to be further explored.

PMID: 17870203 [PubMed - indexed for MEDLINE]

(Via Herbal Science Research aggregator.)

(more…)

The balance of histone acetylation and deacetylation is an index of proliferative activity in many solid tumors. Many botanical agents, especially dietary derived compounds such as the sulfurophanes (eg DIM) from the Brassicaceae can inhibit the enzyme histone deacetylase and modify the ability of DNA to replicate. This is an example of an epigenetic strategy - the actual modification of DNA in the organism, as opposed to “damaging” it. Quite at odds with earlier ideas that gene expression could be modified but that genes could not be. Another valuable non-toxic approach to cancer inhibition.

Biosci Biotechnol Biochem. 2007 Nov;71(11):2712-9Authors: Lee YH, Hong SW, Jun W, Cho HY, Kim HC, Jung MG, Wong J, Kim HI, Kim CH, Yoon HGHistone acetylation depends on the activity of two enzyme families, histone acetyltransferase (HAT) and deacetylase (HDAC). In this study, we screened various plant extracts to find potent HAT inhibitors. Hot water extracts of allspice inhibited HAT activity, especially p300 and CBP (40% at 100 microg/ml). The mRNA levels of two androgen receptor (AR) regulated genes, PSA and TSC22, decreased with allspice treatment (100 microg/ml). Importantly, in IP western analysis, AR acetylation was dramatically decreased by allspice treatment.Furthermore, chromatin immunoprecipitation indicated that the acetylation of histone H3 in the PSA and B2M promoter regions was also repressed. Finally, allspice treatment reduced the growth of human prostate cancer cells, LNCaP (50% growth inhibition at 200 microg/ml). Taken together, our data indicate that the potent HAT inhibitory activity of allspice reduced AR and histone acetylation and led to decreased transcription of AR target genes, resulting in inhibition of prostate cancer cell growth.PMID: 17986787 [PubMed - indexed for MEDLINE

Ginger ingredients reduce viability of gastric cancer cells via distinct mechanisms

Biochem Biophys Res Commun. 2007 Oct 12;362(1):218-23 Authors: Ishiguro K, Ando T, Maeda O, Ohmiya N, Niwa Y, Kadomatsu K, Goto H

Ginger has been used throughout the world as spice, food and traditional herb. We found that 6-gingerol, a phenolic alkanone isolated from ginger, enhanced the TRAIL-induced viability reduction of gastric cancer cells while 6-gingerol alone affected viability only slightly. 6-Gingerol facilitated TRAIL-induced apoptosis by increasing TRAIL-induced caspase-3/7 activation. 6-Gingerol was shown to down-regulate the expression of cIAP1, which suppresses caspase-3/7 activity, by inhibiting TRAIL-induced NF-kappaB activation. As 6-shogaol has a chemical structure similar to 6-gingerol, we also assessed the effect of 6-shogaol on the viability of gastric cancer cells. Unlike 6-gingerol, 6-shogaol alone reduced the viability of gastric cancer cells. 6-Shogaol was shown to damage microtubules and induce mitotic arrest. These findings indicate for the first time that in gastric cancer cells, 6-gingerol enhances TRAIL-induced viability reduction by inhibiting TRAIL-induced NF-kappaB activation while 6-shogaol alone reduces viability by damaging microtubules.

PMID: 17706603 [PubMed - indexed for MEDLINE]

Bad for follicles, good for tumors….

The plant alkaloid sanguinarine is a potential inhibitor of follicular angiogenesis. J Reprod Dev. 2007 Jun;53(3):573-9 Authors: Basini G, Santini SE, Bussolati S, Grasselli F

Sanguinarine (SA), a phytobiotic from Sanguinaria Canadensis, has been demonstrated to inhibit vessel growth. Current restrictions on the use of antibiotic growth promoters have motivated addition of this alkaloid as a naturally appetizing feed additive for farm animals. However, concern may araise since angiogenesis is a fundamental event in ovarian follicle growth. Therefore, the aim of this study was to evaluate the potential negative role of SA in follicular angiogenesis. For this purpose, we studied the effect of 300 nM SA on the production of vascular endothelial growth factor (VEGF) by swine granulosa cells from follicles >5 mm and on the activation of Akt, the main effector of the VEGF signalling pathway. In addition, the potential interference of SA in vessel development was tested in an in vitro angiogenesis bioassay. SA inhibited both VEGF production and VEGF-induced Akt activation in swine granulosa cells. Moreover, it was able to block vessel growth induced by VEGF. Taken together, our results suggest that SA could be detrimental to follicular angiogenesis, and therefore supplementation of feed with this alkaloid should be carefully considered.

PMID: 17310078 [PubMed - indexed for MEDLINE]
[Full-text PDF]

 A useful study for those who mistakenly believe “dairy is pro cancer” ….Full fat raw OG milk (if obtainable)  can be an excellent dietary ingredient for many people, including those with cancer diagnoses.

Calcium, Vitamin D, and Dairy Product Intake and Prostate Cancer Risk
The Multiethnic Cohort Study
Song-Yi Park, Suzanne P. Murphy, Lynne R. Wilkens, Daniel O. Stram, Brian E. Henderson and Laurence N. Kolonel
American Journal of Epidemiology Advance Access published online on October 8, 2007

High intakes of calcium and dairy products have been suggested to be related to prostate cancer risk. Such associations were examined in the Multiethnic Cohort Study (1993–2002) among 82,483 men who completed a detailed quantitative food frequency questionnaire. During a mean follow-up of 8 years, 4,404 total cases of prostate cancer were identified. In Cox proportional hazards models, no association was found between calcium and vitamin D intake and total, advanced, or high-grade prostate cancer risk, whether for total intake, intake from foods, or intake from supplements, among all male participants or among nonusers of supplemental calcium. No association of calcium or vitamin D intake was seen across racial/ethnic groups. In analyses of food groups, dairy product and total milk consumption were not associated with prostate cancer risk. However, low-/nonfat milk was related to an increased risk and whole milk to a decreased risk of total prostate cancer; after stratification, these effects were limited to localized or low-grade tumors. Although the findings from this study do not support an association between the intakes of calcium and vitamin D and prostate cancer risk, they do suggest that an association with milk consumption may vary by fat content, particularly for early forms of this cancer.

Antiproliferative and Apoptotic Effects of Chamomile Extract in Various Human Cancer Cells
Srivastava JK, Gupta S; J Agric Food Chem. 2007 Oct 17;

Chamomile ( Matricaria chamomilla ), a popular herb valued for centuries as a traditional medicine, has been used to treat various human ailments; however, its anticancer activity is unknown. We evaluated the anticancer properties of aqueous and methanolic extracts of chamomile against various human cancer cell lines. Exposure of chamomile extracts caused minimal growth inhibitory responses in normal cells, whereas a significant decrease in cell viability was observed in various human cancer cell lines. Chamomile exposure resulted in differential apoptosis in cancer cells but not in normal cells at similar doses. HPLC analysis of chamomile extract confirmed apigenin 7- O-glucoside as the major constituent of chamomile; some minor glycoside components were also observed. Apigenin glucosides inhibited cancer cell growth but to a lesser extent than the parent aglycone, apigenin. Ex vivo experiments suggest that deconjugation of glycosides occurs in vivo to produce aglycone, especially in the small intestine. This study represents the first reported demonstration of the anticancer effects of chamomile. Further investigations of the mechanism of action of chamomile are warranted in evaluating the potential usefulness of this herbal remedy in the management of cancer patients.

PMID: 17939735

Another of those rare studies on western/southwestern plants: this time aqueous extracts too, showing anticancer activity. The authors are from New Mexico Tech in Socorro NM (in the Biochemical and Biomedical research Lab of the Department of Chemistry and Biology). More please!

Effects of crude aqueous medicinal plant extracts on growth and invasion of breast cancer cells
van Slambrouck S, Daniels AL et al Oncol Rep. 2007 Jun;17(6):1487-92

Plants used in folklore medicine continue to be an important source of discovery and development of novel therapeutic agents. In the present study, we determined the effects of crude aqueous extracts of a panel of medicinal plants on the growth and invasion of cancer cells. Our results showed that extracts of L. tridentata (Creosote Bush) and J. communis L. (Juniper Berry) significantly decreased the growth of MCF-7/AZ breast cancer cells. The latter as well as A. californica (Yerba Mansa) inhibited invasion into the collagen type I gel layer. Furthermore, the phosphorylation levels of extracellular signal-regulated kinase 1 and 2 (ERK1/2) decreased when the cells were exposed to aqueous extracts of L. tridentata, J. communis L. and A. californica. This study provides original scientific data on the anticancer activity of selected aqueous medicinal plant extracts used in traditional medicine.

PMID: 17487409 [PubMed - in process]

Add this to the pile of BC and breast cancer studies. More needed.

Gene expression analysis of the mechanisms whereby black cohosh inhibits human breast cancer cell growth. Einbond LS, Su T, et al. Anticancer Res. 2007 Mar-Apr;27(2):697-712

BACKGROUND: Previous studies indicate that specific extracts and the pure triterpene glycoside actein obtained from black cohosh inhibit growth of human breast cancer cells. Our aim is to identify alterations in gene expression induced by treatment with a methanolic extract (MeOH) of black cohosh. MATERIALS AND METHODS: We treated MDA-MB-453 human breast cancer cells with the MeOH extract at 40 microg/ml and collected RNA at 6 and 24 h; we confirmed the microarray results with real-time RT-PCR for 18 genes. RESULTS: At 6 h after treatment there was significant increase in expression of ER stress (GRP78), apoptotic (GDF15), lipid biosynthetic (INSIG1 and HSD17B7) and Phase 1 (CYP1A1) genes and, at 24 h, decrease in expression of cell cycle (HELLS and PLK4) genes. CONCLUSION: Since the MeOH extract activated genes that enhance apoptosis and repressed cell cycle genes, it may be useful in the prevention and therapy of breast cancer.