Devil's Club Falcarinol-Type Polyacetylenes Inhibit Pancreatic Cancer Cell Proliferation.

Natural falcarinol-type (FC-type) polyacetylenes are known to show anticancer activities. We studied the bioactivity of synthetic FC, 1,2-dihydrofalcarinol (FCH) and 3-acetoxyfalcarinol (FCA) and compared them with the natural bioactive polyacetylene [9,17-octadecadiene-12,14-diyne-1,11,16-triol,1-acetate] (DCA) isolated from Devil's club (DC) Oplopanax horridus. Antiproliferation activity of these polyacetylenes, along with DC inner stem bark 70% ethanol and water extracts, was tested on human pancreatic ductal adenocarcinoma cell lines PANC-1 and BxPC-3. Chemically synthesized FC and FCA showed consistent IC50 (50% inhibition concentration) and higher potency than DCA. FC and DCA's mechanism of action investigated by antibody array on apoptosis-associated genes, and cellular features confirmed by microscopy demonstrated that both compounds modulated genes related to pro-apoptosis, antiapoptosis, apoptosis, cell cycle, stress related, and death receptors. FC-type polyacetylenes with a terminal double bond (FC, FCA, and DCA) are potent inhibitors of pancreatic cancer cell proliferation compared to FCH with a terminal single bond. Liquid chromatography mass spectrometry confirmed the presence of FC and FCH in the inner stem bark of DC. For potential applications of FC-type polyacetylenes as anticancer agents, preparing them by chemical synthesis may provide an advantage over the labor intensive extraction process from raw plant material.

Inhibition of Human Pancreatic Cancer Cell Proliferation by Devil's Club Oplopanax horridus and Its Polyacetylene Bioactive Compound.

Devil's club Oplopanax horridus (DC) is a close relative of ginseng; its inner root and stem bark extract showed antiproliferation activity on human leukemia, ovarian, breast and colon cancer cells. We study here the effects of DC 70% ethanol extract alone, or in combination with cisplatin, gemcitabine, and paclitaxel on pancreatic endocrine HP62 and pancreatic ductal carcinoma PANC-1 and BxPC-3 cells. Antiproliferation activity assay, cell cycle analysis by flow cytometry, apoptosis-related markers by antibody array, and RT-PCR assay were used for this study. DC extract inhibited proliferation of HP62 with IC50 (50% inhibition concentration) at 0.037±0.002% (v/v), PANC-1 at 0.0058 ± 0.0004% and BxPC-3 at 0.021 ± 0.003%. DC at 0.0033% combined with 1 nM of paclitaxel showed inhibition synergy on PANC-1 cells with a combination index of 0.44. Apoptosis focused antibody array profile indicated upregulation of cytochrome C, claspin, cIAP-2 and HTRA2/Omi apoptosis-related markers in DC-treated HP62 and PANC-1. Our data suggest that DC acts through targeting the intrinsic mitochondrial apoptosis pathway in the pancreatic cancer cells. The high antiproliferation potency of DC on PANC-1 is potentially useful as an adjunct therapy for treating pancreatic cancer, which is known for developing resistance to conventional chemotherapeutics.

Human ovarian cancer multicellular spheroids: a model for testing antiproliferation activity of Devil's club (Oplopanax horridus) and anticancer agents.

This study was conducted to employ an ovarian cancer Ovcar 10 three-dimensional model to assess the antiproliferation activity of the medicinal plant Devil's club, Oplopanax horridus, and its active compound, alone and in combination, with chemotherapeutic agents compared to Ovcar 10 two-dimensional cells grown as monolayer cells. Ovcar 10 three-dimensional spheroids were prepared with a rotary cell culture system. Cell counting kit-8 assessed the antiproliferation activity. Apoptosis-related gene expression in three-dimensional spheroids and two- dimensional cells was analyzed with an apoptosis antibody array. Flow cytometry was used to analyze the cell cycle. Ovcar 10 cells formed compact three-dimensional spheroids after 5 days of culture in a rotary culture system. Ovcar 10 three-dimensional spheroids were significantly more resistant to killing by Devil's club extract, its active compound alone, gemcitabine, and paclitaxel, but not cisplatin compared to two-dimensional cells, with IC50 levels closer to that observed in vivo. Devil's club extract and its active compound alone significantly enhanced the antiproliferation activity of cisplatin and gemcitabine at some concentrations, but did not affect the activity of paclitaxel. A number of apoptosis-related genes were differentially expressed in three-dimensional spheroids, two-dimensional cells, and cells treated with Devil's club extract compared to untreated controls. In three-dimensional spheroids, the proportion of cells in the G2/M phase was slightly increased and the S phase was slightly decreased compared to two-dimensional cells. Ovcar 10 cells in three-dimensional spheroids altered the expression of multiple apoptosis-related genes, which may have contributed to the increased resistance of the cells to some drugs.

Antiproliferation effect of Rosemary (Rosmarinus officinalis) on human ovarian cancer cells in vitro.

Rosemary (Rosmarinus officinalis L.) is a popular culinary/medicinal herb. Recent studies have shown it has pharmacologic activities for cancer chemoprevention and therapy. This study evaluated the antiproliferation activity of rosemary extract (RE) against human ovarian cancer cells, and whether the extract and its three main active ingredients carnosol (CS), carnosic acid (CA) and rosmarinic acid (RA) can enhance the antiproliferation activity of cisplatin (CDDP). Our study showed that RE has significant antiproliferation activity on human ovarian cancer A2780 and its CDDP resistant daughter cell line A2780CP70, with IC(50) (50% inhibitory concentration) estimated at 1/1000 and 1/400 dilutions respectively. RE enhanced the antiproliferation effect with CDDP on both A2780 and A2780CP70 cells. A2780 cells were consistently more sensitive to CS, CA, and RA than A2780CP70 cells between 2.5 and 20µg/ml. CS and RA also showed synergistic antiproliferation effect with CDDP on A2780 cells at some concentrations. RE treated by ultrafiltration, dialysis, and removal of phenolics lost the antiproliferation activity suggested that the activity resides in phenolics with MW<1000Da. Apoptosis array study of A2780 cells treated with RE showed that the expression of a number of genes regulating apoptosis were modulated by the treatment. This study showed that RE inhibited the proliferation of ovarian cancer cell lines by affecting the cell cycle at multiple phases. It induced apoptosis by modifying the expression of multiple genes regulating apoptosis, and holds potential as an adjunct to cancer chemotherapy.

Antiproliferation effect of commercially brewed coffees on human ovarian cancer cells in vitro.

Numerous scientific studies have examined the relationship between coffee consumption and an array of medical conditions, including cancer, and yet the direct effect of commercially brewed coffee on cancer cells has not been evaluated. The purpose of this study was to evaluate the antiproliferation effect of 4 different regular and decaffeinated coffee brews and 3 of coffee's bioactive ingredients-caffeine, chlorogenic acids, and caffeic acid-on 2 human ovarian cancer cell lines alone and in combination with cisplatin (CDDP). Antiproliferation IC(50) for Brand A regular and decaffeinated coffee on A2780 cells was 1:70.79 ± 5.66 and 1:55.68 ± 2.00 dilution (vol/vol) in tissue culture medium (mean ± standard error of the mean; N = 12), respectively, and slightly lower on A2780CP70 cells. Three other brands showed lower antiproliferation activity. Antiproliferation IC(50) concentrations of chlorogenic acids and caffeic acid are many folds lower than caffeine. In combination with CDDP, both Brand A coffee brews, and the 3 bioactive compounds, showed additive antiproliferation effect on both cancer cell lines. Flow cytometry analysis showed that coffee treatment induced apoptosis of A2780 and A2780CP70 cells. To our knowledge, this is the first report showing the antiproliferation activity and the additive effect with CDDP of commercially prepared coffee brews on human cancer cell lines.

Inhibition of human ovarian cancer cell lines by devil's club Oplopanax horridus.

AIM OF THE STUDY: To search for more effective treatment of ovarian cancer, we investigated the in vitro anti-proliferation activities of Devil's club (OH) root bark extracts, an important medicinal plant of North America, on cisplatin sensitive and resistant human ovarian cancer cell lines. MATERIALS AND METHODS: High performance liquid chromatography was used to provide the chemical profiling of the OH extracts. The anti-proliferation activities of OH extracts alone or in combination with cisplatin or paclitaxel were determined on four human ovarian cell lines by crystal violet assay. Flow cytometry and light microscopy were employed for cell cycle analysis, and also to detect apoptosis. RESULTS: Our data showed that water, 70% ethanol, 100% ethanol, and ethyl acetate extracts of OH inhibited the proliferation of human ovarian cancer cell lines A2780, A2780CP70, OVCAR3, and OVCAR10 in vitro. The respective 50% inhibition (IC(50)) was estimated at 1/256, 1/74, 1/69, 1/53; 1/4156, 1/1847, 1/1029, 1/4530; 1/25,753, 1/3310, 1/3462, 1/5049; and 1/29,916, 1/2912 1/3828, and 1/4232 dilutions. Some combinations of non-cytotoxic dilutions (

Bioresorbable film for the prevention of adhesion to the anterior spine after anterolateral discectomy.

BACKGROUND CONTEXT: The development of scar tissue and adhesions postoperatively is a natural consequence of healing but can be associated with medical complications and render reoperation difficult. Many biocompatible products have been evaluated as barriers or deterrents to adhesions. PURPOSE: To evaluate the efficacy of a bioresorbable polylactide film as a barrier to adhesion formation after anterolateral discectomy. STUDY DESIGN: Experimental study. METHODS: Seven, skeletally mature female sheep underwent a retroperitoneal approach to the anterolateral lumbar spine. A discectomy was performed at two levels with an intervening unoperated disc site. One site was treated with a polylactide film barrier (Hydrosorb Shield; MacroPore Biosurgery, San Diego, CA) affixed with tacks manufactured from the same material. The second site was left untreated. Treatment and control sites were randomly assigned. Postmortem analysis included scar tenacity scoring on five spines and histological evaluation on two spines. RESULTS: The application of the Hydrosorb film barrier allowed a definite dissection plane during scar tenacity scoring and there was a significant difference in the development of adhesions to the disc between the control and treated sites. Histological evaluation revealed evidence of barrier formation to scar tissue and no significant adverse inflammatory reactions. CONCLUSIONS: Hydrosorb Shield appears to be an effective postoperative barrier to scar tissue adhesion after anterolateral discectomy. The use of polylactide tacks was beneficial to affix the barrier film in place. Safety issues associated with delayed healing or adverse response to the film or tacks were not observed. Hydrosorb film may be useful as an antiadhesion barrier facilitating dissection during surgical revision in anterior approaches to the spine. Further studies are indicated to evaluate the performance of the bioresorbable material as an antiadhesion barrier in techniques of spinal fusion and disc replacement.

Anti-proliferative and antioxidant activities of Saposhnikovia divaricata.

The dry root of Saposhnikovia divaricata (Turcz.) Schischk. (SD, syn. Ledebouriella divaricata (Turcz.); Umbelliferae), Siler, a perennial herb of the carrot family, is also known as Fang Feng in traditional Chinese herbal medicine. It is a herbal ingredient included in many polyherb formulae. This study investigated the in vitro anti-proliferative, antioxidant and anti-inflammatory activities of the SD extract (1 g/10 ml 70% ethanol). IC50 (50% inhibition) is estimated at 1/300, 1/1400, 1/250 and 1/600 dilutions, for the K562, HL60, MCF7 and MDA-MB-468 cell lines, respectively. The combination of non-cytotoxic concentrations of SD with chemotherapeutic drugs such as camptothecin or paclitaxel showed additive anti-proliferative effects on K562, HL60 and MCF7 cells, and antagonistic effects on MDA-MB-468 cells. At a dilution of 1/2000, SD induced a differentiation of 17.5+/-2.5% in HL60 cells along the granulocyte lineage compared to 2.8+/-0.8% in the untreated controls, but not along the monocyte/macrophage lineage. At non-cytotoxic 1/10000, 1/5000 and 1/2000 dilutions, the SD extract did not affect nitric oxide (NO) production by non-stimulated RAW 264.7 cells, but dose-dependently and significantly reduced NO production by lipopolysaccharide (LPS)-activated RAW 264.7 cells. RT-PCR analyses showed that SD at a dilution of 1/2000 did not affect TNFalpha, IL-1 beta, iNOS and COX-2 mRNA expression in RAW 264.7 cells compared to the unstimulated controls, but significantly reduced (p<0.05) iNOS and its mRNA expression in LPS-activated cells. It is concluded that the SD ethanol extract possesses strong anti-proliferative properties against several human tumor cell lines, a mild granulocyte differentiation inducing property on HL60 cells, and potent antioxidant, anti-inflammatory and protective properties on LPS-activated RAW 264.7 cells. Further research is required in order to identify the major ingredients present in the Saposhnikovia divaricata root and rhizome showing the observed activities.

Anti-proliferative and antioxidant properties of rosemary Rosmarinus officinalis.

Constituents in rosemary have shown a variety of pharmacological activities for cancer chemoprevention and therapy in in vitro and in vivo models. In order to further explore the chemopreventive properties of crude extracts of rosemary (Rosmarinus officinalis L), we studied its anti-proliferative property on several human cancer cell lines and its antioxidant and anti-inflammatory properties in vitro in a mouse RAW 264.7 macrophage/monocyte cell line. Our study shows that crude ethanolic rosemary extract (RO) has differential anti-proliferative effects on human leukemia and breast carcinoma cells. The 50% inhibitory concentration (IC50) was estimated at 1/700, 1/400, 1/150 and 1/500 dilutions, for the HL60, K562, MCF7 and MDA-MB-468 cells, respectively. Non-cytotoxic concentrations of RO at 1/1000 dilution minimally induced HL60 cell differentiation into granulocyte lineage at 9.5+/-2.2% compared to 2.8+/-0.8% in the untreated control (p<0.001), and did not induce HL60 cell differentiation into monocyte/macrophage lineage. The 6-hydroxy-2,5,7,8-tetramethyl-chroman-2-carboxylic acid (Trolox) equivalent antioxidant capacity assay showed that RO has substantial antioxidant activity with RO at 1/10 and 1/5 dilutions having 8.1 and 12.6 microM Trolox equivalents, respectively. RO at non-cytotoxic 1/2000 and 1/1000 dilutions did not affect nitric oxide (NO) production by non-stimulated RAW 264.7 cells. However, at the same dilutions RO significantly reduced NO production by lipopolysaccharide (LPS)-activated cells in a dose-dependent manner from 32.6+/-2.3 microM in the LPS-activated cells to 19.2+/-2.2 microM (p<0.01), and 7.7+/-1.2 microM (p<0.001), respectively. RT-PCR analyses showed that RAW 264.7 cells treated with 1/1000 and 1/500 dilutions for 5 h did not affect TNFalpha, IL-1beta, iNOS and COX-2 mRNA expression in these cells when compared to the untreated controls, nor did the 1/1000 dilution of RO affect TNFalpha, IL-1beta, iNOS and COX-2 mRNA expression in the LPS-activated cells. At 1/500 dilution, RO significantly reduced IL-1beta (p<0.01) and COX-2 (p<0.05) mRNA expression and non-significantly reduced TNFalpha and iNOS mRNA expression in the LPS-activated cells. In view of the chemopreventive potentials, further studies are needed to explore other biological properties of this popular spice used by many cultures in the world.

Maoecrystal Z, a cytotoxic diterpene from Isodon eriocalyx with a unique skeleton.

[structure: see text] A novel diterpene with an unprecedented tetracyclic 6,7:8,15-di-seco-7,20-olide-6,8-cyclo-ent-kaurane skeleton, named maoecrystal Z (1), has been isolated from the leaves of a Chinese medicinal herb, Isodon eriocalyx (Labiatae). Its structure was determined by comprehensive NMR and MS spectroscopic analysis coupled with single-crystal X-ray crystallographic diffraction. Compound 1 exhibited comparable inhibitory effect against human K562 leukemia, MCF7 breast, and A2780 ovarian tumor cells with IC(50) = 2.90, 1.63, and 1.45 microg/mL and with camptothecin and paclitaxel as the positive controls.

In vitro anti-proliferative and antioxidant studies on Devil's Club Oplopanax horridus.

Devil's Club, Oplopanax horridus (OH), is a widely used folk medicine in Alaska and British Columbia for treating a variety of ailments including arthritis, fever and diabetes. HPLC profiling shows that numerous compounds are present in the 70% ethanolic extract of OH dry root bark powder. OH extract inhibited K562, HL60, MCF7 and MDA-MB-468 cell growth with the 50% inhibition (IC(50)) estimated at 1/2700, 1/1700, 1/500 and 1/2500 dilutions, respectively. Non-cytotoxic concentrations (

Stability and cytotoxicity of gambogic acid and its derivative, gambogoic acid.

In this study, the stability of gambogic acid (GA), a polyprenylated xanthone with potent cytotoxicities against various cancer cell lines, was evaluated under several experimental conditions including addition of acids, alkalis and organic solvents. GA was stable when dissolved in acetone, acetonitrile, and chloroform, even when acids were added. However, a new derivative was produced after GA was stored in the methanol solution for a week at room temperature. The addition of alkalis could increase the rate of this chemical transformation. This derivative was determined to be gambogoic acid (GOA) by the HPLC-MS comparison with the known compound. GOA was proposed to be the product of neuclophilic addition of methanol to the olefinic bond at C-10 of GA. Furthermore, when these two compounds were tested for their cytotoxicity, GOA showed significantly weaker inhibitory effects than GA. It was therefore deduced that the alpha,beta-unsaturated carbonyl moiety at C-10 contributed to the cytotoxicity of gambogic acid.

In vitro studies of the dry fruit of Chinese fan palm Livistona chinensis.

The hot water extract of the dry fruit of Chinese fan palm Livistona chinensis R Br. (LC) has been used in folklore medicine in Southern China for treating various tumors. Our in vitro study showed that the ethanolic extract (LCET) and the hot water extract (LCWE) of LC inhibited HL60 cell growth, with 50% inhibition (IC(50)) estimated at a 1/50 dilution for both preparations. LCET showed mild activity in inducing HL60 cell differentiation into granulocyte lineage. However, at 1/100 and 1/200 dilutions, it respectively induced 32.4+/-12.6% and 16.3+/-6.1% of HL60 cells into monocyte/macrophage lineage, compared to 4.4+/-1.3% in the control. In contrast, LCWE did not demonstrate a significant differentiation-inducing capacity on HL60 cells. Cell-free Trolox equivalent antioxidant capacity hydroxyl radical scavenging assay estimated that a 1/10 dilution of LCET and LCWE has a similar activity, equivalent to 13.0 and 12.7 microM of Trolox activity respectively. At a 1/100 dilution, neither extract affected nitric oxide production in both non-stimulated and lipopolysaccharide (LPS) stimulated RAW 264.7 cells. RT-PCR analyses of mRNA expression showed that treatment of RAW 264.7 cells with either extract at a 1/100 dilution did not affect tumor necrosis factor-alpha (TNFalpha), interleukin-1beta (IL-1beta), inducible nitric oxide synthase (iNOS) and cyclo-oxygenase-2 (COX-2) mRNA expression in these cells compared to the untreated control. Neither extract affected TNFalpha and iNOS mRNA expression in LPS-stimulated cells, but at a 1/100 dilution they both reduced IL-1beta mRNA expression in LPS-stimulated cells (p<0.01). Only a 1/100 dilution of LCET reduced COX-2 mRNA expression in LPS-stimulated RAW 264.7 cells (p<0.01). The dry fruit of Livistona chinensis warrants further investigation.

Antioxidant and anti-inflammatory properties of ESSIAC and Flor-Essence.

Essiac (ES) and Flor-Essence (FE) are two herbal teas widely taken by North American cancer patients during chemo- and radiation-therapy. The antioxidant and anti-inflammatory properties of these two herbal teas were assessed in this study. Cell-free Trolox equivalent antioxidant capacity assay shows that at 1/5 dilution, ES and FE have hydroxyl radical scavenging activity equivalent to 10.65 microM and 5.74 microM of Trolox respectively. Treatment with ES at 1/10 and 1/20 dilutions significantly increased nitric oxide (NO) production by murine RAW 264.7 cells, but inhibited NO production in a concentration-dependent manner by lipopolysaccharide (LPS)-stimulated cells. In contrast, FE at 1/10 and 1/20 dilutions did not significantly induce NO production by RAW 264.7 cells, nor did it, at these dilutions, inhibit the NO production by LPS-stimulated RAW 264.7 cells. RT-PCR assay shows that both 1/20 and 1/100 dilutions of ES and FE induced mRNA expression of IL-1beta, inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) pro-inflammatory molecules in RAW 264.7 cells compared to untreated controls. Addition of ES and FE at 1/20 and 1/100 dilutions to LPS-stimulated RAW 264.7 cells did not alter IL-1beta, iNOS and COX-2 mRNA expression in these cells. ES and FE treatment did not affect TNFalpha mRNA expression in non-stimulated or LPS-stimulated RAW 264.7 cells. Our data show that ES but not FE stimulated NO release by non-stimulated and inhibited LPS-stimulated RAW 264.7 cells. There were only minor differences between ES and FE in their induction of mRNA expression of pro-inflammatory molecules. Further research is needed to investigate the differential activities of these two herbal teas in stimulating pro-inflammatory mediators release by RAW 264.7 cells.

In Vitro culture studies of FlorEssence on human tumor cell lines.

FlorEssence (FE) is an herbal tea widely used by patients to treat chronic conditions in North America, particularly cancer patients during chemo- and radiation therapy. Although individual components of FE have antioxidant, antiestrogenic, immunostimulant and antitumor properties, in vitro evidence of anticancer activity for the herbal tea itself is still lacking. We studied the antiproliferative effect of FE on MCF7 and MDA-MB-468 human breast cancer, and Jurkat and K562 leukemia cell lines. We found that FE significantly inhibited the proliferation of both breast and leukemia cells in vitro only at high concentrations, with 50% inhibition of MDA-MB-468 cells at about 1[sol ]20 dilution, Jurkat cells at about 1[sol ]10 dilution and MCF7 and K562 cells at less than 1[sol ]10 dilution. Flow cytometry analysis showed that treatment with a high concentration of FE induced G2[sol ]M arrest in MCF7 and Jurkat cells, with also an increased SubG0[sol ]G1 fraction in MCF7 cells. MDA-MB-468 cells showed a significantly increased Sub G0[sol ]G1 fraction after treatment with 1[sol ]10 dilution of FE while the cell cycle of K562 was unaffected. When MCF7 and MDA-MB-468 breast cancer cells were treated with a combination of FE with either paclitaxel or cisplatin, results showed that only the combination of 1[sol ]20 dilution of FE with 0.5 microM cisplatin resulted in a small but significantly higher MCF7 cell survival than 0.5 microM cisplatin treatment alone. FE at 1[sol ]20 and 1[sol ]50 dilutions did not affect the antiproliferative properties of these two commonly used chemotherapeutic agents. The results suggest that FE at high concentrations show differential inhibitory effect on different human cancer cell lines. Further studies are needed to assess the biological activities of FE.

Tumor necrosis factor-related apoptosis-inducing ligand and CD56 expression in patients with type 1 diabetes mellitus.

OBJECTIVES: Our previous report showed that beta-cell antigen-specific CD56+ T-cells and cytokine TRAIL mediate destruction of human pancreatic [beta] cells in vitro. To determine whether CD56 and TRAIL are present during islet cell destruction at the onset of clinical symptoms of type 1 diabetes mellitus (T1D), we studied cell marker and cytokine expression in the pancreatic islets of 2 children who died at presentation of acute-onset T1D and in T-cell lines derived from a group of children with new-onset T1D. METHODS: TRAIL, CD56, and other T-cell markers and cytokine expression were studied using immunohistochemistry on pancreatic sections from 2 children with acute-onset T1D. TRAIL and CD56 expression was analyzed by flow cytometry in the antigen-activated T-cell lines derived from 29 children with new-onset T1D. RESULTS: TRAIL+, CD56+, CD45RO+, and CD3+ cells were present in the islets of acute-onset T1D patients, while none were present in the normal islets. T-cell lines from new-onset T1D expressed TRAIL and CD56 in response to stimulation with beta-cell antigens GAD, IA-2 and insulin beta chain. CONCLUSION: The presence of TRAIL and CD56 markers is part of the T-cell response repertoire in beta-cell destruction.

In vitro culture studies of Sutherlandia frutescens on human tumor cell lines.

Sutherlandia frutescens is a South African herb used traditionally by the natives to treat cancer, and more recently to improve the overall health in HIV/AIDS patients. Gas chromatography/mass spectrometer profiling and liquid chromatographic/mass spectral investigation confirmed and quantified the presence of canavanine, GABA and arginine in the herbal preparation used in this study. In vitro study demonstrated a concentration dependent effect of Sutherlandia on several tumor cell lines, with 50% inhibition (IC50) of proliferation of MCF7, MDA-MB-468, Jurkat and HL60 cells at 1/250, 1/200, 1/150 and 1/200 dilutions, respectively. Sutherlandia treatment did not induce HL60 differentiation along the macrophage/monocyte or granulocyte lineage. It demonstrated antioxidant activity in reducing free radical cations with an estimated activity of 0.5 microl of Sutherlandia extract equivalent to that of 10 microM of Trolox. However, it did not significantly suppress lipopolysaccharide stimulated nitric oxide production by murine macrophage/monocyte RAW 264.7 cells, nor did it significantly inhibit IL-1beta and TNF-alpha mRNA expression in RAW 264.7 cells. In conclusion, Sutherlandia ethanolic extract showed a concentration dependent antiproliferative effect on several human tumor cell lines but did not show significant antioxidant effects. Further studies are needed to explore the activities of this multipurpose South African herbal preparation.

Use of polylactide resorbable film as a barrier to postoperative peridural adhesion in an ovine dorsal laminectomy model.

OBJECT: The purpose of this study was to evaluate the performance of a resorbable polylactide film in the sheep posterior spine in the presence of a combined laminectomy and durotomy defect. METHODS: A resorbable polylactide film was used to cover the combined defects in the eight sheep used in this study. Two surgical levels were performed in each animal, with randomly assigned control and treated sites. Each surgical level consisted of a full laminectomy followed by a needle-induced durotomy. The treated levels received a resorbable polylactide film cut to size and tucked in under the laminar defect. At 8 to 10 weeks postoperatively, results of myelography and visual dye infiltration showed complete healing of the durotomies for all sites. In addition, evaluation of gross dissection based on volume and tenacity scores as well as histological findings indicates decreased posterior dural adhesions for sites treated with resorbable polylactide film. CONCLUSIONS: The results of this investigation support previous studies in which the use of a resorbable polylactide film was found to be effective in reducing posterior dural adhesions in the spine with no apparent safety issues related to impaired dural healing.

In vitro comparison of Essiac and Flor-Essence on human tumor cell lines.

Essiac (ES) and Flor-Essence (FE) are two herbal teas widely taken by North American cancer patients during chemo- and radiation therapy. In vitro studies on the antiproliferative and differentiation inducing activities of these teas were performed. ES and FE showed negligible antiproliferative activity on Jurkat leukemia cells. Both herbal teas inhibited 50% (IC50) of MCF7 breast cancer cell growth at 1/10 dilution. The IC50 was about 1/40 and 1/10 dilution of FE and ES respectively for MDA-MB-468 human breast cancer cells. The IC50 for HL60 cells was at 1/10 dilution of FE and less than 1/10 dilution of ES. ES at 1/10 dilution induced expression of non-specific esterase in 16% of HL60 cells, compared to about 5% in FE treated cells and untreated controls. ES treatment of HL60 cells induced 47-67% nitroblue tetrazolium positive staining cells compared to 24.6+/-3.1% in cells treated with 1/10 dilution of FE. Flow cytometry analysis showed that both ES and FE treatment between 1/10 and 1/100 dilutions only slightly affected the cell cycle progression of MCF7, MDA-MB-468, Jurkat and HL60 cells. Our data show that both ES and FE herbal teas demonstrated antiproliferative and differentiation inducing properties in vitro only at high concentrations. Further research is needed to elucidate the in vivo activities.