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Sagar NA, Pareek S, Benkeblia N, Xiao J. Onion (
Allium cepa
L.) bioactives: Chemistry, pharmacotherapeutic functions, and industrial applications. FOOD FRONTIERS 2022. [DOI: 10.1002/fft2.135] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022] Open
Affiliation(s)
- Narashans Alok Sagar
- Department of Agriculture and Environmental Sciences National Institute of Food Technology Entrepreneurship and Management Kundli Sonepat Haryana India
| | - Sunil Pareek
- Department of Agriculture and Environmental Sciences National Institute of Food Technology Entrepreneurship and Management Kundli Sonepat Haryana India
| | - Noureddine Benkeblia
- Department of Life Sciences/The Biotechnology Centre The University of the West Indies Kingston Jamaica
| | - Jianbo Xiao
- Nutrition and Bromatology Group Department of Analytical and Food Chemistry Faculty of Sciences Universidade de Vigo Ourense Spain
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Baba-Ahmed F, Guedri K, Trea F, Ouali K. Protective role of a melon superoxide dismutase combined with gliadin (GliSODin) on the status of lipid peroxidation and antioxidant defense against azoxymethane-induced experimental colon carcinogenesis. J Cancer Res Ther 2021; 17:1445-1453. [PMID: 34916376 DOI: 10.4103/jcrt.jcrt_175_19] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022]
Abstract
Background Azoxymethane (AOM) is a potent carcinogenic agent commonly used to induce colon cancer in rats and mice, with the cytotoxicity of AOM mediated by oxidative stress. Aim of Study This study investigated the protective effect of a natural antioxidant (GliSODin) against AOM-induced oxidative stress and carcinogenesis in rat colon. Methods Twenty male Wistar rats were randomly divided into four groups (five rats/group). The control group was fed a basal diet. AOM-treated group (AOM) was fed a basal diet and received intraperitoneal injections of AOM for 2 weeks at a dose of 15 mg/kg. The GliSODin treatment group (superoxide dismutase [SOD]) received oral supplementation of GliSODin (300 mg/kg) for 3 months, and the fourth combined group received AOM and GliSODin (AOM + SOD). All animals were continuously fed ad libitum until the age of 16 weeks when all rats were sacrificed. The colon tissues were examined microscopically for pathological changes and aberrant crypt foci (ACF) development, oxidant status (lipid peroxidation-LPO), and enzyme antioxidant system (glutathione [GSH], GSH-S-transferase, catalase, and SOD). Results Our results showed that AOM induced ACF development and oxidative stress (GSH depletion and lipid peroxidation) in rat colonic cells. The concomitant treatment of AOM with GliSODin significantly ameliorated the cytotoxic effects of AOM. Conclusion The results of this study provide in vivo evidence that GliSODin reduced the AOM-induced colon cancer in rats, through their potent antioxidant activities.
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Affiliation(s)
- Fedia Baba-Ahmed
- Department of Biology University El hadj Lakhder-Batna, University El Hadj Lakhder-Batna, Batna, Algeria
| | - Kamilia Guedri
- Department of Biology, University of Tebessa, University Larbi Tebessi, Tebessa, Algeria
| | - Fouzia Trea
- Department of Animal Biology University, University of Badji Mokhtar Annaba, Laboratory of Environmental Bio Surveillance, University of Badji Mokhtar-Annaba, Annaba, Algeria
| | - Kheireddine Ouali
- Department of Animal Biology University, University of Badji Mokhtar Annaba, Laboratory of Environmental Bio Surveillance, University of Badji Mokhtar-Annaba, Annaba, Algeria
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Ahmad R, Khan MA, Srivastava A, Gupta A, Srivastava A, Jafri TR, Siddiqui Z, Chaubey S, Khan T, Srivastava AK. Anticancer Potential of Dietary Natural Products: A Comprehensive Review. Anticancer Agents Med Chem 2020; 20:122-236. [DOI: 10.2174/1871520619666191015103712] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2018] [Revised: 06/21/2019] [Accepted: 07/02/2019] [Indexed: 02/07/2023]
Abstract
Nature is a rich source of natural drug-like compounds with minimal side effects. Phytochemicals
better known as “Natural Products” are found abundantly in a number of plants. Since time immemorial, spices
have been widely used in Indian cuisine as flavoring and coloring agents. Most of these spices and condiments
are derived from various biodiversity hotspots in India (which contribute 75% of global spice production) and
form the crux of India’s multidiverse and multicultural cuisine. Apart from their aroma, flavor and taste, these
spices and condiments are known to possess several medicinal properties also. Most of these spices are mentioned
in the Ayurveda, the indigenous system of medicine. The antimicrobial, antioxidant, antiproliferative,
antihypertensive and antidiabetic properties of several of these natural products are well documented in
Ayurveda. These phytoconstituemts are known to act as functional immunoboosters, immunomodulators as well
as anti-inflammatory agents. As anticancer agents, their mechanistic action involves cancer cell death via induction
of apoptosis, necrosis and autophagy. The present review provides a comprehensive and collective update
on the potential of 66 commonly used spices as well as their bioactive constituents as anticancer agents. The
review also provides an in-depth update of all major in vitro, in vivo, clinical and pharmacological studies done
on these spices with special emphasis on the potential of these spices and their bioactive constituents as potential
functional foods for prevention, treatment and management of cancer.
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Affiliation(s)
- Rumana Ahmad
- Department of Biochemistry, Era’s Lucknow Medical College & Hospital, Era University, Sarfarazganj, Lucknow-226003, UP, India
| | - Mohsin A. Khan
- Chancellor, Era University, Sarfarazganj, Hardoi Road, Lucknow-226003, UP, India
| | - A.N. Srivastava
- Department of Pathology, Era’s Lucknow Medical College & Hospital, Era University, Sarfarazganj, Lucknow-226003, UP, India
| | - Anamika Gupta
- Department of Biochemistry, Era’s Lucknow Medical College & Hospital, Era University, Sarfarazganj, Lucknow-226003, UP, India
| | - Aditi Srivastava
- Department of Biochemistry, Era’s Lucknow Medical College & Hospital, Era University, Sarfarazganj, Lucknow-226003, UP, India
| | - Tanvir R. Jafri
- Department of Biochemistry, Era’s Lucknow Medical College & Hospital, Era University, Sarfarazganj, Lucknow-226003, UP, India
| | - Zainab Siddiqui
- Department of Pathology, Era’s Lucknow Medical College & Hospital, Era University, Sarfarazganj, Lucknow-226003, UP, India
| | - Sunaina Chaubey
- Department of Biochemistry, Era’s Lucknow Medical College & Hospital, Era University, Sarfarazganj, Lucknow-226003, UP, India
| | - Tahmeena Khan
- Department of Chemistry, Integral University, Dasauli, P.O. Bas-ha, Kursi Road, Lucknow 226026, UP, India
| | - Arvind K. Srivastava
- Department of Food and Nutrition, Era University, Sarfarazganj, Lucknow-226003, UP, India
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Abstract
The Allium genus includes garlic, onions, shallots, leeks, and chives. These vegetables are popular in cuisines worldwide and are valued for their potential medicinal properties. Epidemiologic studies, while limited in their abilities to assess Allium consumption, indicate some associations of Allium vegetable consumption with decreased risk of cancer, particularly cancers of the gastrointestinal tract. Limited intervention studies have been conducted to support these associations. The majority of supportive evidence on Allium vegetables cancer-preventive effects comes from mechanistic studies. These studies highlight potential mechanisms of individual sulfur-containing compounds and of various preparations and extracts of these vegetables, including decreased bioactivation of carcinogens, antimicrobial activities, and redox modification. Allium vegetables and their components have effects at each stage of carcinogenesis and affect many biologic processes that modify cancer risk. This review discusses the cancer-preventive effects of Allium vegetables, particularly garlic and onions, and their bioactive sulfur compounds and highlights research gaps.
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Affiliation(s)
- Holly L Nicastro
- Cancer Prevention Fellowship Program, Nutritional Science Research Group, Division of Cancer Prevention, National Cancer Institute, Bethesda, MD.
| | - Sharon A Ross
- Nutritional Science Research Group, Division of Cancer Prevention, National Cancer Institute, Bethesda, Maryland
| | - John A Milner
- USDA/ARS Beltsville Human Nutrition Research Center, Beltsville, Maryland
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Turati F, Guercio V, Pelucchi C, La Vecchia C, Galeone C. Colorectal cancer and adenomatous polyps in relation to allium vegetables intake: a meta-analysis of observational studies. Mol Nutr Food Res 2014; 58:1907-14. [PMID: 24976533 DOI: 10.1002/mnfr.201400169] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2014] [Revised: 04/29/2014] [Accepted: 05/05/2014] [Indexed: 01/24/2023]
Abstract
SCOPE To provide updated quantitative estimates of the associations between allium vegetables intake and risk of colorectal cancer and colorectal adenomatous polyps. METHODS AND RESULTS We combined all published data on the issue, using a meta-analytic approach. Pooled relative risks (RRs) were calculated using random-effects models. Sixteen studies (13 333 cases) were included in the meta-analyses of colorectal cancer. Seven studies provided information on garlic, six on onion, and four on total allium vegetables. The pooled RRs of colorectal cancer for the highest versus the lowest category of intake were 0.85 (95% confidence interval; CI, 0.72-1.00) for garlic (0.76 for case-control, 0.99 for cohort studies), 0.85 (95% CI, 0.70-1.04) for onion (0.74 for case-control, 1.04 for cohort studies), and 0.78 (95% CI, 0.56-1.08) for total allium vegetables. Significant heterogeneity was found for the three meta-analyses. The pooled RR of colorectal adenomatous polyps for the highest versus the lowest category of total allium vegetables intake was 0.88 (95% CI, 0.80-0.98, three studies), with no heterogeneity. CONCLUSION High garlic intake may reduce the risk of colorectal cancer. However, evidence of such protection derived mainly from case-control studies. High intake of total allium vegetables may be associated with a risk reduction of colorectal adenomatous polyps.
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Affiliation(s)
- Federica Turati
- Department of Epidemiology, IRCCS-Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy
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Shirshova TI, Beshlei IV, Deryagina VP, Ryzhova NI, Matistov NV. Chemical composition of Allium schoenoprasum leaves and inhibitory effect of their extract on tumor growth in mice. Pharm Chem J 2013. [DOI: 10.1007/s11094-013-0867-8] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
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Srimuangwong K, Tocharus C, Tocharus J, Suksamrarn A, Yoysungnoen Chintana P. Effects of hexahydrocurcumin in combination with 5-fluorouracil on dimethylhydrazine-induced colon cancer in rats. World J Gastroenterol 2012; 18:6951-9. [PMID: 23322993 PMCID: PMC3531679 DOI: 10.3748/wjg.v18.i47.6951] [Citation(s) in RCA: 30] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/07/2012] [Revised: 09/17/2012] [Accepted: 09/22/2012] [Indexed: 02/06/2023] Open
Abstract
AIM: To investigate the effects of hexahydrocurcumin (HHC), and its combination with 5-fluorouracil (5-FU) on dimethylhydrazine (DMH)-induced colon cancer in rats.
METHODS: Male Wistar rats weighing 100-120 g were used as subject models. Aberrant crypt foci (ACF), early preneoplastic lesions of colon cancer, were induced by subcutaneous injection of DHM (40 mg/kg) twice a week for two weeks. After the first DMH injection, rats were treated daily with vehicle (n = 12), curcumin (CUR) (50 mg/kg) (n = 12), HHC (50 mg/kg) orally (n = 12), and treated weekly with an intraperitoneal injection of 5-FU (50 mg/kg) (n = 12), or a combination of 5-FU plus CUR (n = 12) and HHC (n = 12) at the same dosage(s) for 16 wk. The total number of ACF and large ACF were assessed. Cyclooxygenase (COX)-1 and COX-2 expression were detected by immunohistochemistry in colon tissues. The quantitative data of both COX-1 and COX-2 expression were presented as the percentage of number of positive-stained cells to the total number of cells counted. Apoptotic cells in colon tissues were also visualized using the dUTP-biotin nick end labeling method. Apoptotic index (AI) was determined as the percentage of labeled nuclei with respect to the total number of nuclei counted.
RESULTS: The total number of ACF was highest in the DMH-vehicle group (1558.20 ± 17.37), however, the number of ACF was significantly reduced by all treatments, 5-FU (1231.20 ± 25.62 vs 1558.20 ± 17.37, P < 0.001), CUR (1284.20 ± 25.47 vs 1558.20 ± 17.37, P < 0.001), HHC (1086.80 ± 53.47 vs 1558.20 ± 17.37, P < 0.001), DMH-5-FU + CUR (880.20 ± 13.67 vs 1558.20 ± 17.37, P < 0.001) and DMH-5-FU + HHC (665.80 ± 16.64 vs 1558.20 ± 17.37, P < 0.001). Interestingly, the total number of ACF in the combined treatment groups, the DMH-5-FU + CUR group (880.20 ± 13.67 vs 1231.20 ± 25.62, P < 0.001; 880.20 ± 13.67 vs 1284.20 ± 25.47, P < 0.001) and the DMH-5-FU + HHC group (665.80 ± 16.64 vs 1231.20 ± 25.62, P < 0.001; 665.80 ± 16.64 vs 1086.80 ± 53.47, P < 0.001) were significantly reduced as compared to 5-FU or each treatment alone. Large ACF were also significantly reduced in all treatment groups, 5-FU (111.00 ± 7.88 vs 262.20 ± 10.18, P < 0.001), CUR (178.00 ± 7.33 vs 262.20 ± 10.18, P < 0.001), HHC (186.60 ± 21.51 vs 262.20 ± 10.18, P < 0.001), DMH-5-FU + CUR (122.00 ± 5.94 vs 262.20 ± 10.18, P < 0.001) and DMH-5-FU + HHC (119.00 ± 17.92 vs 262.20 ± 10.18, P < 0.001) when compared to the vehicle group. Furthermore, in the DMH-5-FU + CUR and DMH-5-FU + HHC groups the formation of large ACF was significantly reduced when compared to CUR (122.00 ± 5.94 vs 178.00 ± 7.33, P < 0.005) or HHC treatment alone (119.00 ± 17.92 vs 186.60 ± 21.51, P < 0.001), however, this reduction was not statistically different to 5-FU monotherapy (122.00 ± 5.94 vs 111.00 ± 7.88, P = 0.217; 119.00 ± 17.92 vs 111.00 ± 7.88, P = 0.619, respectively). The levels of COX-1 protein after all treatments were not different from normal rats. A marked increase in the expression of COX-2 protein was observed in the DMH-vehicle group. Over-expression of COX-2 was not significantly decreased by 5-FU treatment alone (95.79 ± 1.60 vs 100 ± 0.00, P = 0.198). However, over-expression of COX-2 was significantly suppressed by CUR (77.52 ± 1.68 vs 100 ± 0.00, P < 0.001), HHC (71.33 ± 3.01 vs 100 ± 0.00, P < 0.001), 5-FU + CUR (76.25 ± 3.32 vs 100 ± 0.00, P < 0.001) and 5-FU + HHC (68.48 ± 2.24 vs 100 ± 0.00, P < 0.001) in the treated groups compared to the vehicle group. Moreover, CUR (77.52 ± 1.68 vs 95.79 ± 1.60, P < 0.001), HHC (71.33 ± 3.01 vs 95.79 ± 1.60, P < 0.001), 5-FU + CUR treatments (76.25 ± 3.32 vs 95.79 ± 1.60, P < 0.001) and 5-FU + HHC (68.48 ± 2.24 vs 95.79 ± 1.60, P < 0.001) markedly decreased COX-2 protein expression more than 5-FU alone. Furthermore, the AI in all treated groups, 5-FU (38.86 ± 4.73 vs 23.56 ± 2.12, P = 0.038), CUR (41.78 ± 6.92 vs 23.56 ± 2.12, P < 0.001), HHC (41.06 ± 4.81 vs 23.56 ± 2.12, P < 0.001), 5-FU + CUR (49.05 ± 6.75 vs 23.56 ± 2.12, P < 0.001) and 5-FU + HHC (53.69 ± 8.59 vs 23.56 ± 2.12, P < 0.001) significantly increased when compared to the DMH-vehicle group. However, the AI in the combination treatments, 5-FU + CUR (49.05 ± 6.75 vs 41.78 ± 6.92, P = 0.192; 49.05 ± 6.75 vs 38.86 ± 4.73, P = 0.771) and 5-FU + HHC (53.69 ± 8.59 vs 41.06 ± 4.81, P = 0.379; 53.69 ± 8.59 vs 38.86 ± 4.73, P = 0.245) did not reach significant levels as compared with each treatment alone and 5-FU monotherapy, respectively.
CONCLUSION: The combined effects of HHC with 5-FU exhibit a synergistic inhibition by decreasing ACF formation mediated by down-regulation of COX-2 expression.
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Klewicka E, Nowak A, Zduńczyk Z, Juśkiewicz J, Cukrowska B. Protective effect of lactofermented red beetroot juice against aberrant crypt foci formation, genotoxicity of fecal water and oxidative stress induced by 2-amino-1-methyl-6-phenylimidazo[4,5-b] pyridine in rats model. ENVIRONMENTAL TOXICOLOGY AND PHARMACOLOGY 2012; 34:895-904. [PMID: 22995401 DOI: 10.1016/j.etap.2012.08.009] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/15/2012] [Accepted: 08/23/2012] [Indexed: 06/01/2023]
Abstract
The aim of the study was to investigate the effects of beetroot juice fermented by Lactobacillus brevis 0944 and Lactobacillus paracasei 0920 (FBJ) on carcinogen induction of aberrant crypt foci (ACF) in rat colon. 2-Amino-1-methyl-6-phenylimidazo[4,5-b] pyridine (PhIP) was used as carcinogen, which was administrated intragastrically at a dose of 10 μg/day, every day of the experiment. Additionally, we investigated the cytotoxicity and genotoxicity of fecal water from experimental animals in the Caco-2 cell line, evaluated by MTT test and the comet assay, respectively, as well as by the count of bacteria adhered to colon epithelium assessed by fluorescence in situ hybridization. Oxidative stress in rats was expressed by measuring serum antioxidant status and the level of malondialdehyde in the kidneys and liver. The experimental rats were divided into four groups based on diet type: basal diet, basal diet supplemented with FBJ, basal diet and PhIP treatment, and basal diet supplemented with FBJ and PhIP treatment. FBJ significantly reduced the number of ACF in PhIP-treated rats (from 59 ± 18 to 26 ± 4). Moreover, the number of extensive aberrations (more than 4 crypts in a focus) decreased from 52 ± 18 to 18 ± 4. Fecal water obtained from rats fed with a PhIP-containing diet induced pronounced cytotoxic and genotoxic effects in Caco-2 cells, but FBJ supplementation of the diet abolished these effects. In groups fed dietary PhP and FBJ the latter was found to increase the antioxidant status of serum from 40% to 66% depending on the fraction. Reduced concentration of malondialdehyde was found only in the kidneys of rats fed with PhIP and FBJ. FBJ present in the diet of rats causes a reduction of MDA in the kidneys from 118.7 nmol/g tissue to 100 nmol/g tissue. The presence of FBJ in the diet of rats significantly increased the count of bacteria, including Lactobacillus/Enterococcus and Bacteroides-Prevotella group adhered to colonic epithelium. In conclusion, supplementation of the diet with lactofermented beetroot juice may provide protection against precancerous aberrant crypt formation and reduce the cytotoxic and genotoxic effects of fecal water and improve the oxidative status of the organism.
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Affiliation(s)
- Elżbieta Klewicka
- Institute of Fermentation Technology and Microbiology, Technical University of Lodz, Department of Biotechnology and Food Science, Wolczanska 171/173, 90-924 Lodz, Poland.
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Zhou AC, Jin HY, Tan XZ, Qian XL, Zhang CX, He YS, Wang SM. Allium cepa extracts inhibit the proliferation of colorectal cancer in vitro. Shijie Huaren Xiaohua Zazhi 2011; 19:2011-2015. [DOI: 10.11569/wcjd.v19.i19.2011] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To determine the contents of flavonoids in water and alcohol extracts of Allium cepa and to investigate their inhibitory effect on the proliferation of colorectal cancer cells.
METHODS: The contents of flavonoids extracted from Allium cepa with water and alcohol were determined by ultraviolet-visible spectroscopy. Colorectal cancer cells (Lovo cells, SW480 cells, HT-29 cells and HCT-8 cells) were cultured in vitro and incubated with different concentration of flavonoids (0, 2.5, 5, 10, 20, 40, 60, 80 mg/L). Cell proliferation was tested by WST-8 assay.
RESULTS: The content of flavonoids was higher than in the water extract of Allium cepa than in the alcohol extract. Both the water and alcohol extracts of Allium cepa inhibited the proliferation of colorectal cancer cells in a dose- and time-dependent manner. The water extract of Allium cepa had a more significant inhibitory effect on cell proliferation than the alcohol extract (10 mg/L: 37.77 ± 5.84 vs 17.36 ± 5.24; 20 mg/L: 52.35 ± 5.72 vs 24.15 ± 5.54; 40 mg/L: 68.17 ± 7.76 vs 32.79 ± 6.02; 60 mg/L: 71.08 ± 8.16 vs 47.55 ± 2.45; 80 mg/L: 76.00 ± 5.87 vs 60.35 ± 6.61, all P < 0.05).
CONCLUSION: Allium cepa extracts can significantly inhibit the proliferation of colorectal cancer cells.
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Tian WX, Ma XF, Zhang SY, Sun YH, Li BH. Fatty acid synthase inhibitors from plants and their potential application in the prevention of metabolic syndrome. ACTA ACUST UNITED AC 2011. [DOI: 10.1007/s11805-011-0550-3] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/25/2022]
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Chidambara Murthy KN, Jayaprakasha GK, Kumar V, Rathore KS, Patil BS. Citrus limonin and its glucoside inhibit colon adenocarcinoma cell proliferation through apoptosis. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2011; 59:2314-2323. [PMID: 21338095 DOI: 10.1021/jf104498p] [Citation(s) in RCA: 64] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/30/2023]
Abstract
The current study was an attempt to elucidate the mechanism of human colon cancer cell proliferation inhibition by limonin and limonin glucoside (LG) isolated from seeds of Citrus reticulata. The structures of purified compounds were confirmed by NMR and quantified using HPLC. These compounds of more than 95% purity were subjected to proliferation inhibition assay using human colon adenocarcinoma (SW480) cells. The IC50 value of 54.74 and 37.39 μM was observed for limonin and LG, respectively at 72 h. Following confirmation of proliferation inhibition, pattern of DNA fragmentation and activation of caspase-3 of the cells treated with limonoids suggest involvement of apoptosis. Furthermore, reduction in the transcription ratio of bcl2/bax and induction of cytochrome c release from mitochondria to cytosol with treatment of limonoids confirm the activation of intrinsic apoptosis pathway. The activity of Bax and Bcl2 was confirmed through analysis of mitochondrial membrane potential and intracellular calcium in the cells treated with limonin and LG; the net content of caspase-8 was not affected by limonoids. Results of the current study provide compelling evidence on the induction of mitochondria mediated intrinsic apoptosis by both limonin and LG in cultured SW480 cells for the first time.
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Affiliation(s)
- Kotamballi N Chidambara Murthy
- Vegetable and Fruit Improvement Center, Department of Horticultural Sciences, Texas A&M University, College Station, Texas 77845-2119, United States
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Klewicka E, Nowak A, Zduńczyk Z, Cukrowska B, Błasiak J. Protective effect of lactofermented beetroot juice against aberrant crypt foci formation and genotoxicity of fecal water in rats. ACTA ACUST UNITED AC 2010; 64:599-604. [PMID: 21185162 DOI: 10.1016/j.etp.2010.12.001] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2010] [Revised: 11/02/2010] [Accepted: 12/01/2010] [Indexed: 12/19/2022]
Abstract
The aim of the study was to investigate the effects of beetroot juice fermented by Lactobacillus brevis 0944 and Lactobacillus paracasei 0920 (FBJ) on carcinogen induction of aberrant crypt foci (ACF) in rat colon. N-Nitroso-N-methylurea (MNU) was used as carcinogen, which was administrated intragastrically at a dose of 50 mg/kg on the 23rd and 26th day of the experiment. Additionally, we investigated the cytotoxicity and genotoxicity of fecal water from experimental animals in the Caco 2 cell line, evaluated by MTT/NRU tests and the comet assay, respectively, as well as by the count of bacteria adhered to colon epithelium assessed by fluorescence in situ hybridization and DAPI staining. The experimental rats were divided into four groups based on diet type: basal diet, basal diet supplemented with FBJ, basal diet and MNU treatment, and basal diet supplemented with FBJ and MNU treatment. FBJ significantly reduced the number of ACF in MNU-treated rats (from 55±18 to 21±6). Moreover, the number of extensive aberrations (more than 4 crypts in a focus) decreased from 45±21 to 7±4. Fecal water obtained from rats fed with an MNU-containing diet induced pronounced cytotoxic and genotoxic effects in Caco 2 cells, but FBJ supplementation of the diet abolished these effects. The presence of FBJ in the diet significantly increased the count of bacteria, including Lactobacillus/Enterococcus, adhered to colonic epithelium. In conclusion, supplementation of the diet with lactofermented beetroot juice may provide protection against precancerous aberrant crypt formation and reduce the cytotoxic and genotoxic effects of fecal water.
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Affiliation(s)
- Elżbieta Klewicka
- Institute of Fermentation Technology and Microbiology, Technical University of Lodz, Department of Biotechnology and Food Science, Wolczanska 171/173, 90-924 Lodz, Poland.
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Winning H, Roldán-Marín E, Dragsted LO, Viereck N, Poulsen M, Sánchez-Moreno C, Cano MP, Engelsen SB. An exploratory NMR nutri-metabonomic investigation reveals dimethyl sulfone as a dietary biomarker for onion intake. Analyst 2009; 134:2344-51. [PMID: 19838425 DOI: 10.1039/b918259d] [Citation(s) in RCA: 50] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/10/2023]
Abstract
The metabolome following intake of onion by-products is evaluated. Thirty-two rats were fed a diet containing an onion by-product or one of the two derived onion by-product fractions: an ethanol extract and the residue. A 24 hour urine sample was analyzed using (1)H NMR spectroscopy in order to investigate the effects of onion intake on the rat metabolism. Application of interval extended canonical variates analysis (ECVA) proved to be able to distinguish between the metabolomic profiles from rats consuming normal feed and rats fed with an onion diet. Two dietary biomarkers for onion intake were identified as dimethyl sulfone and 3-hydroxyphenylacetic acid. The same two dietary biomarkers were subsequently revealed by interval partial least squares regression (PLS) to be perfect quantitative markers for onion intake. The best PLS calibration model yielded a root mean square error of cross-validation (RMSECV) of 0.97% (w/w) with only 1 latent variable and a squared correlation coefficient of 0.94. This indicates that urine from rats on the by-product diet, the extract diet, and the residue diet all contain the same dietary biomarkers and it is concluded that dimethyl sulfone and 3-hydroxyphenylacetic acid are dietary biomarkers for onion intake. Being able to detect specific dietary biomarkers is highly beneficial in the control of nutritionally enhanced functional foods.
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Affiliation(s)
- Hanne Winning
- University of Copenhagen, Faculty of Life Sciences, Dept. of Food Science, Quality & Technology, Rolighedsvej 30, 1958 Frederiksberg C, Denmark
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Abstract
Onions are excellent sources of bioactive compounds including fructo-oligosaccharides (FOS) and polyphenols. An onion by-product was characterised in order to be developed as a potentially bioactive food ingredient. Our main aim was to investigate whether the potential health and safety effects of this onion by-product were shared by either of two derived fractions, an extract containing the onion FOS and polyphenols and a residue fraction containing mainly cell wall materials. We report here on the effects of feeding these products on markers of potential toxicity, protective enzymes and gut environment in healthy rats. Rats were fed during 4 weeks with a diet containing the products or a control feed balanced in carbohydrate. The onion by-product and the extract caused anaemia as expected in rodents for Allium products. No other toxicity was observed, including genotoxicity. Glutathione reductase (GR) and glutathione peroxidase (GPx1) activities in erythrocytes increased when rats were fed with the onion extract. Hepatic gene expression of Gr, Gpx1, catalase, 5-aminolevulinate synthase and NAD(P)H:quinone oxidoreductase was not altered in any group of the onion fed rats. By contrast, gamma-glutamate cysteine ligase catalytic subunit gene expression was upregulated but only in rats given the onion residue. The onion by-products as well as the soluble and insoluble fractions had prebiotic effects as evidenced by decreased pH, increased butyrate production and altered gut microbiota enzyme activities. In conclusion, the onion by-products have no in vivo genotoxicity, may support in vivo antioxidative defence and alter the functionality of the rat gut microbiota.
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Ziliotto L, Pinheiro F, Barbisan LF, Rodrigues MAM. Screening for in vitro and in vivo antitumor activities of the mushroom Agaricus blazei. Nutr Cancer 2009; 61:245-50. [PMID: 19235041 DOI: 10.1080/01635580802395717] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/13/2023]
Abstract
We have investigated the in vitro antitumor activity of the mushroom Agaricus blazei Murill on human cancer cell lines as well as its potential anticancer activity in a model of rat colon carcinogenesis. The in vitro anticancer analysis was performed using 9 human cancer cell lines incubated with organic and aqueous extracts of A. blazei. Antitumor activity was observed with the dichloromethane/methanol and hexanic extracts of A. blazei at 250 mu g/ml for all cancer cell lines tested. No antiproliferative/cytotoxic activities were detected for the aqueous, methanol, ethyl acetate, or n-butanolic extracts. In the in vivo analysis, crude A. blazei was given orally after carcinogen treatment in a rat medium-term study (20 weeks) of colon carcinogenesis using aberrant crypt foci (ACF) as biomarker. Male Wistar rats were given dimethylhydrazine (DMH) and then were fed A. blazei at 5% in the diet until Week 20. ACF were scored for number and crypt multiplicity. A. blazei intake did not suppress ACF development or crypt multiplicity induced by DMH. No differences in tumor incidence in the colon were observed among the DMH-treated groups. Our results indicate that employing A. blazei in the diet does not have a suppressive effect on colon carcinogenesis.
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Affiliation(s)
- Liane Ziliotto
- Department of Pathology, Botucatu Medical School, UNESP/São Paulo State University, São Paulo, Brazil
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16
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Ziliotto L, Barbisan LF, Rodrigues MAM. Lack of chemoprevention of dietary Agaricus blazei against rat colonic aberrant crypt foci. Hum Exp Toxicol 2008; 27:505-11. [PMID: 18784204 DOI: 10.1177/0960327108091862] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/13/2023]
Abstract
The mushroom Agaricus blazei (Ab) has been widely used in folk medicine to treat various diseases including cancer. No information is available on its possible protective effects on the development of colon cancer. The potential blocking effect of Ab intake on the initiation stage of colon carcinogenesis was investigated in a short-term (4-week) bioassay using aberrant crypt foci (ACF) as biomarker. Male Wistar rats were given four subcutaneous injections of the carcinogen 1,2-dimethylhydrazine (DMH, 40 mg/kg bw, twice a week), during 2 weeks to induce ACF. The diet containing Ab at 5% was given 2 weeks before and during carcinogen treatment to investigate the potential beneficial effects of this edible mushroom on DMH-induced ACF. All groups were killed at the end of the fourth week. The colons were analyzed for ACF formation in 1% methylene blue whole-mount preparations and for cell proliferation in histological sections immunohistochemically stained for the proliferating cell nuclear antigen (PCNA). All DMH-treated rats developed ACF mainly in the middle and distal colon. Agaricus blazei intake at 5% did not alter the number of ACF induced by DMH or the PCNA indices in the colonic mucosa. Thus, the results of the present study did not confirm a chemopreventive activity of Ab on the initiation stage of rat colon carcinogenesis.
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Affiliation(s)
- L Ziliotto
- Department of Pathology, Botucatu Medical School, UNESP Sao Paulo State University, Botucatu, SP, Brazil
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17
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Rajamanickam S, Agarwal R. Natural products and colon cancer: current status and future prospects. Drug Dev Res 2008; 69:460-471. [PMID: 19884979 DOI: 10.1002/ddr.20276] [Citation(s) in RCA: 116] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/16/2023]
Abstract
Carcinogenesis is a multistage process consisting of initiation, promotion and progression phases. Thus, the multistage sequence of events has many phases for prevention and intervention. Chemoprevention, a novel approach for controlling cancer, involves the use of specific natural products or synthetic chemical agents to reverse, suppress or prevent premalignancy before the development of invasive cancer. Several natural products, such as, grains, nuts, cereals, spices, fruits, vegetables, beverages, medicinal plants and herbs and their various phytochemical constituents including, phenolics, flavonoids, carotenoids, alkaloids, nitrogen containing as well as organosulfur compounds confer protective effects against wide range of cancers including colon cancer. Since diet has an important role in the etiology of colon cancer, dietary chemoprevention received attention for colon cancer prevention. However, identification of an agent with chemopreventive potential requires in vitro studies, efficacy and toxicity studies in animal models before embarking on human clinical trials. A brief introduction about colon cancer and the role of some recent natural products in colon cancer chemoprevention with respect to multiple molecular mechanisms in various in vitro, in vivo and clinical studies are described in this review.
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Affiliation(s)
- Subapriya Rajamanickam
- Department of Pharmaceutical Sciences, School of Pharmacy, University of Colorado Denver, Denver, Colorado, USA
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