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ABSTRACT: Male Hi-Myc mice were placed on three dietary regimens [30% calorie restriction (CR), overweight control (modified AIN76A with 10 kcal% fat), and a diet-induced obesity regimen (DIO) 60 kcal% fat]. All diet groups had approximately similar incidence of hyperplasia and low-grade prostatic intraepithelial neoplasia in the ventral prostate at 3 and 6 months of age. However, 30% CR significantly reduced the incidence of in situ adenocarcinomas at 3 months compared with the DIO group and at 6 months compared with both the overweight control and DIO groups. Furthermore, the DIO regimen significantly increased the incidence of adenocarcinoma with aggressive stromal invasion, as compared with the overweight control group (96% vs. 65%, respectively; P = 0.02) at the 6-month time point. In addition, at both 3 and 6 months, only in situ carcinomas were observed in mice maintained on the 30% CR diet. Relative to overweight control, DIO increased whereas 30% CR reduced activation of Akt, mTORC1, STAT3, and NFκB (p65) in ventral prostate. DIO also significantly increased (and 30% CR decreased) numbers of T-lymphocytes and macrophages in the ventral prostate compared with overweight control. The mRNA levels for interleukin (IL) 1α, IL1β, IL6, IL7, IL23, IL27, NFκB1 (p50), TNFα, and VEGF family members were significantly increased in the ventral prostate of the DIO group compared with both the overweight control and 30% CR diet groups. Collectively, these findings suggest that enhanced growth factor (Akt/mTORC1 and STAT3) and inflammatory (NFκB and cytokines) signaling may play a role in dietary energy balance effects on prostate cancer progression in Hi-Myc mice.
Cancer Prevention Research 09/2011; 4(12):2002-14. · 4.91 Impact Factor
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ABSTRACT: Murraya paniculata is a common plant widely available in Bangladesh. Different parts of the plant have been used extensively in various traditional formulations in South Asian countries. In order to rationalize the traditional use of the bark of M. paniculata, extract of equal proportions of petroleum ether, ethyl acetate and methanol was subject to mice, to evaluate its analgesic activities. The extract of the bark of M. paniculata obtained by cold extraction at an oral dose of 200 and 400 mg/kg body weight significantly and dose dependently reduced the frequency of acetic acid induced writhing and prolonged the tail flicking latency in mice. At the given doses, the extract showed 37 (p<0.001) and 45% (p<0.001) inhibition of writhing respectively. In radiant heat tail-flicking method the crude extract produced 56 (p<0.001) and 73% (p<0.001) elongation of flicking time after 30 min and 30 (p<0.01) and 41% (p<0.001) elongation of flicking time 60 min after oral doses of 200 and 400 mg/kg body weight respectively. On the other hand, the bark extract exhibited 19% (p<0.05) elongation of flicking time after 120 min.
International Journal of Medicine and Medical Sciences. 05/2011; 3:105-108.
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ABSTRACT: Green tea is now recognized as the most effective cancer preventive beverage. In one study, 10 Japanese-size cups of green tea daily supplemented with tablets of green tea extract limited the recurrence of colorectal polyps in humans to 50%. Thus, cancer patients who consume green tea and take anticancer drugs will have double prevention. We studied the effects of combining (-)-epigallocatechin gallate (EGCG) and anticancer drugs, focusing on inhibition of cell growth and induction of apoptosis. Numerous anticancer drugs, such as tamoxifen, COX-2 inhibitors, and retinoids were used for the experiments, and the combination of EGCG and COX-2 inhibitors consistently induced the enhancement of apoptosis. To study the mechanism of the enhancement, we paid special attention to the enhanced expressions of DDIT3 (growth arrest and DNA damage-inducible 153, GADD153), GADD45A, and CDKN1A (p21/WAF1/CIP1) genes, based on our previous evidence that a combination of EGCG and sulindac specifically induced upregulated expression of GADD153 and p21 genes in PC-9 lung cancer cells. The synergistic enhancements of apoptosis and GADD153 gene expression in human non-small cell lung cancer cells by the combination of EGCG and celecoxib were mediated through the activation of the MAPK signaling pathway. This article reviews the synergistic enhancement of apoptosis, gene expression, and anticancer effects using various combinations of EGCG and anticancer drugs, including the combination of (-)-epicatechin (EC) and curcumin. Based on the evidence, we present a new concept: green tea catechins as synergists with anticancer drugs.
Cancer Science 02/2011; 102(2):317-23. · 3.33 Impact Factor
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ABSTRACT: Curcumin, a phenolic compound isolated from the plant Curcuma longa (Linn), is ingested every day in the Indian subcontinent and is well reported to possess cancer-preventive activity. To achieve effective cancer prevention with curcumin, we need to find a new method to enhance the effects of curcumin in the diet. Based on our evidence that (-)-epicatechin (EC), an inert catechin, enhances the cancer-preventive activity of green tea catechins, we studied the enhancing effects of EC on inductions of growth inhibition and apoptosis in human lung cancer cell lines PC-9 and A549 with curcumin. The combination of curcumin with EC significantly increased the inhibition of cell growth compared with curcumin or EC alone. The combination similarly increased both apoptosis and expression of GADD153 and GADD45 genes, associated with their enhanced protein production. Knockdown of GADD153 or GADD45 by small interfering RNA abrogated the apoptosis induction and growth inhibition induced by the combination, indicating the crucial role of their upregulation. Treatments of PC-9 cells with c-Jun-NH(2)-kinase inhibitor SP600125, with p38 mitogen-activated protein kinase inhibitor SB202190 and with PD98059 (extracellular signal-regulated kinase 1/2 inhibitor) all increased the upregulation of GADD153 and GADD45 genes by the combination. Because EC was previously shown to enhance the incorporation of EGCG into PC-9 cells, we think that EC has similar effects on curcumin. This report is the first report on the enhancing effects of EC on curcumin, and the data suggest that EC plays a significant role in the enhancement of the cancer-preventive activity of curcumin in the diet.
Cancer Prevention Research 08/2010; 3(8):953-62. · 4.91 Impact Factor
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ABSTRACT: The expression of "growth arrest and DNA damage inducible genes 45 and 153" is related to apoptotic induction of cells. GADD45 is an effector gene of the tumor suppressor p53, and GADD153 is associated with cellular function of cancer prevention. Curcumin, isolated from the plant Curcuma longa (LINN), has been investigated as a promising cancer preventive in food because curcumin, a phenolic and coloring compound, is widely ingested in the Indian subcontinent. However, the exact mechanisms of action of curcumin have not yet been clearly elucidated. Based on our successful results with green tea catechins as cancer preventive, we studied the relationship between the expression of GADD45 and 153 and apoptotic induction in human lung cancer cell line PC-9. In our study curcumin increased the expression of GADD45 and 153 in a p53-independent manner. Curcumin also inhibited the growth of PC-9 cells and induced G(1)/S arrest of the cell-cycle followed by strong induction of apoptosis. Treatment with GADD45 and 153 small interfering RNAs (siRNAs) inhibited the apoptotic induction in PC-9 cells by curcumin. Moreover, curcumin induced the expression of cyclin dependent kinase inhibitor genes p21 and p27, while it inhibited the expression of numerous genes, including Bcl-2, cyclin D1, CDK2, CDK4 and CDK6. All the results with PC-9 cells suggest that the up-regulation of GADD45 and 153 by curcumin is a prime mechanism in the anticancer activity of curcumin.
Biological & Pharmaceutical Bulletin 01/2010; 33(8):1291-9. · 1.66 Impact Factor
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ABSTRACT: The extract of the bark of Albizia lebbeck Benth. obtained by cold extraction of mixture of equal proportions of petroleum ether, ethyl acetate and methanol was chosen for pharmacological screening. In rat paw edema model induced by carrageenan, the extract at the 400 mg/kg dose level showed 36.68% (p<0.001) inhibition of edema volume at the end of 4h. In the acetic acid-induced writhing test, the extract at the 200 and 400 mg/kg dose level showed 39.9% and 52.4 % inhibition of writhing, respectively. In radiant heat tail-flick method the crude extract produced 40.74% (p<0.001) and 61.48% (p<0.001) elongation of tail flicking time 30 minutes after oral administration at the 200 and 400 mg/kg dose level, respectively.
Pakistan journal of pharmaceutical sciences 01/2009; 22(1):74-7. · 1.10 Impact Factor
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ABSTRACT: The analgesic and anti-inflammatory activities of a new alkaloid, 1,2,3,9-tetrahydro-pyrrolo [2,1-b] quinazolin-3-ylamine (compound 1) isolated from Sida cordifolia Linn. were investigated in animal models. In the acetic acid induced writhing model, the compound 1 showed 25.4 (P<0.05) and 52.43% (P<0.01) inhibition of writhing response at doses of 25 and 50 mg/kg body weight respectively. The alkaloid also produced significant increase in the tail flick latency in radiant heat tail-flick method. In Carrageenan induced rat paw edema the compound 1 produced 16.93 and 24.43 % inhibition of paw edema at the doses of 25 and 50 mg/kg body weight respectively at the third hour of study.
Pakistan journal of pharmaceutical sciences 08/2007; 20(3):185-8. · 1.10 Impact Factor
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ABSTRACT: Successive hexane, chloroform and methanol extracts of the rhizome of Hedychium coronarium Koen. (HC) were subjected to evaluate analgesic and anti-inflammatory activities in animal model. In acetic acid-induced writhing test, the chloroform and methanol extract at doses of 400 mg/kg body weight elicited 27.23 and 40.59% inhibition of writhing reflex respectively. Both the chloroform and methanol extracts showed significant elongation of tail flick time (41.15 and 61.32% elongation respectively) at 400 mg/kg body weight. In carrageenan induced rat paw edema test, the chloroform and methanol extracts at a dose of 400 mg/kg body weight showed statistically significant (P<0.01) inhibition of paw edema by 27.46 and 32.48%, respectively at the third hour after carrageenan injection.
Pakistan journal of pharmaceutical sciences 01/2007; 20(1):47-51. · 1.10 Impact Factor
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ABSTRACT: The hexane (PLH), ethyl acetate (PLE) and methanol (PLM) extracts of dried whole plant parts of Polygonum lanatum Roxb. (Family, Polygonaceae) obtained by successive cold extraction, were subjected to evaluate anti-inflammatory, analgesic and diuretic activity in experimental animals. Oral administration of either PLH and PLM at a dose of 300 mg/kg body weight showed statistically significant (p < 0.001) inhibition of rat paw edema by 41.09% and 30.15%, respectively, which was comparable to that of standard drug phenylbutazone (42.15%). Compared to the inhibition of acetic acid-induced writhing by aminopyrine (69.94%, p < 0.001), treatment with either PLH, PLE or PLM elicited significant inhibition of acetic acid-induced writhing reflex by 44.80% (p < 0.001), 33.87% (p < 0.01) and 62.29% (p < 0.001), respectively. In addition, mild to potent diuretic activity was observed after oral administration of these extracts in Swiss albino mice.
Pakistan journal of pharmaceutical sciences 10/2005; 18(4):13-8. · 1.10 Impact Factor
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ABSTRACT: In the present study, the analgesic and anti-inflammatory activities of a new alkaloid (5'-Hydroxymethyl-1'-(1,2,3,9-tetrahydro-pyrrolo [2,1-b] quinazolin-1-yl)-heptan-1-one) (compound 1), isolated from Sida cordifolia Linn. was investigated in animal models. The analgesic activity was investigated in the acetic acid induced writhing and the radiant heat tail flick model in mice and the carrageenan induced rat paw edema model was used for anti-inflammatory study. The compound produced significant (p<0.01) analgesic activity in both models. The compound also exhibited significant (p<0.01) inhibition of rat paw edema induced by carrageenan. These results indicated that compound 1 possessed analgesic and anti-inflammatory activities.
Iranian Journal of Pharmacology and Therapeutics (ISSN: 1735-2657) Vol 5 Num 2.