Pyrene-induced Lung Carcinogenesis Research Articles

Chemopreventive effect of chrysin, a dietary flavone against benzo(a)pyrene induced lung carcinogenesis in Swiss albino mice

Chemoprevention is considered as one of the most promising and realistic approaches in the prevention of lung cancer. Chrysin, a naturally occurring dietary flavone widely found in Passiflora family of plants and honey, has been studied extensively for its chemopreventive properties. The objective of present study is to divulge the chemopreventive role of chrysin against benzo(a)pyrene [B(a)P] induced lung carcinogenesis in Swiss albino mice. B(a)P was administered orally (50mg/kg body weight) twice a week for four weeks to induce lung cancer in mice. The body weight, lung weight, tumor incidence, lipid peroxidation, carcinoembryonic antigen, enzymatic antioxidants (superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase) and non-enzymatic antioxidants (reduced glutathione, vitamin E and vitamin C) were estimated. Further, histopathological analysis of lung tissue and western blotting analysis of PCNA, COX-2 and NF-κB were also carried out. Administration of B(a)P resulted in increased lipid peroxides and carcinoembryonic antigen with concomitant decrease in the levels of both enzymatic antioxidants and non-enzymatic antioxidants. Chrysin treatment (250mg/kg body weight) significantly attenuated all these changes thereby showing potent anti lung cancer effect. Further, the anticancer effect of chrysin was confirmed by histopathology of lungs, and immunoblotting analysis of PCNA, COX-2 and NF-κB, where chrysin supplementation downregulated the expression of these proteins and maintained cellular homeostasis. Overall, these findings confirm the chemopreventive potential of chrysin against B(a)P induced lung cancer in Swiss albino mice.

Curcumin and quercetin trigger apoptosis during benzo(a)pyrene-induced lung carcinogenesis.

The aim of the present study was to assess the cumulative effects of curcumin and quercetin in inducing apoptosis during benzo(a)pyrene (BP) (100 mg/Kg body weight)-induced lung carcinogenesis in mice. BP treatment resulted in a significant increase in the protein expression of Bcl-2 whereas expression of Bax was significantly decreased. Further, BP treatment brought about a significant decrease in the activities of caspase 3, caspase 9 as well as the number of apoptotic cells. Interestingly, separate as well as combined supplementation of curcumin (60 mg/kg body weight) and quercetin (40 mg/kg body weight) to BP-treated animals resulted in a significant decrease in the protein expression of Bcl-2 but caused a significant increase in the protein expression of Bax along with a noticeable improvement in the number of apoptotic cells. Also, supplementation with curcumin and quercetin separately to BP-treated mice brought a significant improvement in the enzyme activities of caspase 9 as well as caspase 3 but the improvement was more pronounced following combined treatment. Therefore, curcumin and quercetin, if given in combination shall exhibit enhanced chemopreventive potential against development of lung carcinogenesis by stimulating the apoptotic machinery.

Protective role of Solanum trilobatum (Solanaeace) against benzo(a)pyrene-induced lung carcinogenesis in Swiss albino mice

ObjectiveTo investigate the protective effect of leaf extract of Solanum trilobatum (ELEST) against benzo(a)pyrene (BP) induced lung carcinogenesis. MethodsExperiment was designed with the treatment regimen of ELEST [200mg/kg body weight dissolved in dimethyl sulphoxide(DMSO)] for 4weeks before (pre-initiation) and from 12th week after B(a)P (50mg/kg body weight) induced lung carcinoma(post-initation). ResultsAdministration of BP (50mg/kg body weight) resulted in increased lipid peroxidation (LPO) and marker enzymes, such as arylhydrocarbon hydroxylase (AHH), gamma-glutamyl transpeptidase (γGT), 5′-nucleotidase (5′ND) and lactate dehydrogenase (LDH) along with decrease in the levels of tissue antioxidants, like superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), reduced glutathione (GSH), vitamin E and vitamin C in mice. Significantly, ELEST modulated these alterations suggest the efficacy of ELEST in the chemotherapeutics of lung cancer. The histopathological studies also evidenced the protective efficiency of the extract against lung carcinogenesis. Further, significant increase in the levels of Cytochrome P450, Cytochrome b5, NADPH Cyt c reductase and decrease in UDP-glucuronyl transferase and quinone reductase was observed in microsomal fraction of lung and liver of BP-induced mice, whereas the treatment with ELEST resulted in reversal of modulations observed in the activities of detoxification enzymes. ConclusionsCollectively, the present observations indicate that the treatment with ELEST exhibited protective and antioxidant effect against BP-induced lung carcinogenesis.

The potency of essential nutrient taurine on boosting the antioxidant status and chemopreventive effect against benzo (a)pyrene induced experimental lung cancer

Lung cancer is a major cause of morbidity and mortality worldwide both in men and women accounting for 29% of all other cancers. The constituents of smoke consist of polycyclic aromatic hydrocarbons (PAHs) such as benzo(a)pyrene which play a major role in lung carcinogenesis. B(a)P increases oncogenic stimulation by enhancing intrinsic ROS stress and metabolic activity. Recent focus of cancer chemoprevention is on the supplementation of natural anti-oxidants which are capable of ameliorating biochemical and molecular changes that occur during carcinogenesis. Taurine (2-aminoethanesulfonic acid), a sulfur-containing β-amino acid abundant in sea foods has potent antioxidant property. The present study was framed to investigate the potency of taurine on boosting the antioxidant status and chemopreventive effect against benzo(a)pyrene induced lung carcinogenesis in Swiss albino mice. Administration of B(a)P (50mg/kg body weight) to mice resulted in decrease in the activities of enzymic and non-enzymic anti-oxidants with concomitant increase in lipid peroxides (LPO), protein carbonyls and lung specific tumor markers. Taurine supplementation (100mg/kg body weight) significantly attenuated these alterations. From these results, we suggest that administration of B(a)P induces ROS production and diminishes antioxidant levels. Conversely, taurine affords protection from ROS induced lung damage by augmenting the function of anti-oxidants.

Immunomodulatory Effect of Mangiferin in Experimental Animals with Benzo(a)Pyrene-induced Lung Carcinogenesis

The immunomodulatory activity of mangiferin was studied in various groups of animals. For this study, adult Swiss albino male mice were treated with benzo(a)pyrene, abbreviated as B(a)P, at 50 mg/kg body weight orally twice a week for 4 weeks; and mangiferin was also given orally (pre- and post-initiation of carcinoma) at 100 mg/kg body weight. Immunocompetence and immune complexes as measured by phagocyte index, avidity index, and soluble immune complex (SIC) levels (p<0.001), as well as NBT reduction, were decreased in the B(a)P-treated animals;whereas increased levels of immunocompetence were noted in the mangiferin-treated animals given B(a)P (p<0.001, p<0.05). The levels of immunoglobulins such as IgG and IgM were decreased considerably (p<0.001) in the B(a)P-treated animals compared with their levels in the control animals; whereas the IgA level was increased (p<0.001). In the mangiferin-treated experimental animals given B(a)P, the levels of IgG and IgM were significantly (p<0.001, p<0.05) increased whereas the IgA level was decreased compared with those for the B(a)P-treated mice. Oxidative changes in lymphocytes, neutrophils, and macrophages were also measured. The enhanced lipid peroxidation and decreased catalase and superoxide dismutase activities found in the lymphocytes, polymorphonuclear cells (PMN), and macrophages from B(a)P-treated mice were significantly reduced and increased, respectively, by the mangiferin treatment. This study confirms the immunomodulatory effect of mangiferin and shows an immunoprotective role arbitrated through a reduction in the reactive intermediate-induced oxidative stress in lymphocytes, neutrophils, and macrophages.

Anticancer activity of esculetin via-modulation of Bcl-2 and NF-κB expression in benzo[a]pyrene induced lung carcinogenesis in mice

Esculetin (ESC), a coumarin derivative, has shown to possess antioxidant, anti-inflammatory, anticancer and chemopreventive properties. In the present study, we evaluated the chemopreventive activity of ESC against benzo[a]pyrene (B[a]P) induced lung carcinogenesis in Swiss albino mice by measuring antioxidant parameter, like lipid peroxidation, reduced glutathione (GSH) and superoxide dismutase (SOD); and levels of Bcl-2 and NF-κB protein in lung tissues. Lung carcinogenesis was induced by B[a]P (50mg/kg, intraperitoneally). Pre-treatment and post-treatment groups were treated with ESC (50mg/kg, per oral). Oxidative stress-induced by B[a]P was decreased by ESC. Anti-apoptotic protein Bcl-2 and pleotropic regulator NF-κB are found to possess oncogenic roles in B[a]P induced carcinogenesis. Western blot analysis study showed alleviated levels Bcl-2 and NF-κB in ESC pre-treated and post-treated groups in comparison to B[a]P treated group. These results suggest the anti-initiating and apoptosis inducing property of ESC on pre- and post-treatment in B[a]P induced lung carcinogenesis in Swiss albino mice.

COX-2 as a Potential Target in Chemoprevention of Benzo(a)pyrene Induced Lung Carcinogenesis in Mice-combined Role of Curcumin and Quercetin

The present study was undertaken to assess the cumulative effects of curcumin and quercetin in inhibiting the activity of COX-2 alongwith other biophysical parameters such as 3 H thymidine uptake as well as uptake and turnover of 14 C-glucose during BP induced lung carcinogenesis in mice. The mice were segregated into five groups viz., normal control, BP treated, BP + curcumin treated, BP + quercetin treated and BP + curcumin+ quercetin treated. Lung carcinogenesis was induced by a single intra-peritoneal (IP) injection of BP (100mg/Kg body weight). Curcumin and quercetin were supplemented to mice at dose levels of 60mg/Kg body weight and 40mg/Kg body wt in drinking water, respectively. All the treatments were continued for a period of 22 weeks. BP treatment brought about a significant increase in the activities of COX-2. Supplementation of phytochemicals individually as well in combination to BP treated mice brought about moderation in the enzymatic activity which was restored to within normal limits. Further, BP treatment recorded increased 3 H thymidine uptake as well as enhanced 14 C-glucose uptake and its turnover which were reduced significantly following simultaneous treatment with phytochemicals. Therefore, cumulative treatment with curcumin and quercetin has the potential of providing protection against lung cancer by inhibiting the COX-2 activity and moderating the 3 H thymidine uptake as well as 14 C-glucose uptake and its turnover.

Capsaicin inhibits benzo(a)pyrene-induced lung carcinogenesis in an in vivo mouse model

Lung cancer is a serious health problem in most developed countries and its incidence rate is profusely increasing. Capsaicin, a component of red chilli and red pepper has been studied widely for its chemopreventive properties. The aim of the present study is to explore the anti-tumor activity of capsaicin against benzo(a)pyrene-induced lung tumorigenesis in Swiss albino mice. Benzo(a)pyrene was administered orally (50 mg/kg body weight) to induce lung cancer in Swiss albino mice. Hematological study (hemoglobin content, RBC, WBC count and differential count), histochemical analysis of mast cells and Western blot analysis of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), cyclooxygenase-2 (COX-2) and nuclear factor-kappa B (NF-κB) were carried out. Hematological parameters and the histochemical analysis of mast cells showed abnormal changes, and the immunoblotting analysis revealed increased protein expression of TNF-α, IL-6, COX-2 and NF-κB in lung cancer-challenged mice administered with benzo(a)pyrene. Capsaicin (10 mg/kg body weight) supplementation to lung cancer bearing mice considerably prevented all the above abnormalities. The results of the present study indicate the protective effect of capsaicin against benzo(a)pyrene-induced lung carcinogenesis in mice.

Premature Mitochondrial Senescence and Related Ultrastructural Changes during Lung Carcinogenesis Modulation by Curcumin and Resveratrol

The present study attempted to explore the efficacy of curcumin and resveratrol in modulating premature mitochondria senescence and ultrastructural changes during lung carcinogenesis. The mice were segregated into 5 groups, which included normal control, benzo[a]pyrene (BP) treated, BP + curcumin (C) treated, BP + resveratrol (R) treated, and BP + C + R treated groups. Animals were given a single ip injection of benzo[a]pyrene in corn oil at a dose level of 100 mg/kg body weight. Treatments of curcumin and resveratrol were given orally in drinking water at a dose level of 60 mg/kg body weight and 5.7 µg/mL drinking water, respectively, 3 times a week for a total duration of 22 weeks. Ultrastructure of BP-treated mice revealed disruptions in cellular integrity along with nuclear deformation and premature mitochondrial senescence. Interestingly, supplementation of curcumin and resveratrol individually resulted in improvement of ultrahistoarchitecture of BP-treated mice but the improvement was much greater with combined supplementation of phytochemicals. Further, benzo[a]pyrene treatment revealed alterations in lung histoarchitecture, which, however, was improved appreciably following combined supplementation with curcumin and resveratrol. The present study concludes that combined supplementation with curcumin and resveratrol effectively modulates histoarchitecture as well as ultrahistoarchitecture during benzo[a]pyrene-induced lung carcinogenesis in mice.Cancer is a public health problem worldwide []. Lung cancer is a major cause of mortality throughout the world and is responsible for the deaths of more than one million people annually []. Phytochemicals have shown great potential in preventing the occurrence of cancer and other chronic diseases that result from oxidative stress induced by free radicals []. Phytochemicals are nonnutritive products of plants and, being nontoxic, are presently being studied the world over for their chemopreventive actions in controlling various diseases, including cancer. In the present study, curcumin and resveratrol are the phytochemicals of interest. Curcumin, a polyphenol, has been reported to have anti-invasive properties []. Further, curcumin has been shown to activate apoptotic machinery in patients with lung cancer []. On the other hand, resveratrol (trans-3,4,5- thihydroxystibene) is a phytoalexin that is present naturally in grapes as well as in a variety of medicinal plants and has been shown to exhibit antioxidant activity with a potential to induce apoptosis [].

Baicalein improves antioxidant status and membrane-bound enzymes during oxidative stress in benzo(a)pyrene-induced lung carcinogenesis in mice

The chemopreventive efficacy of baicalein (BE) flavanoid during benzo(a)pyrene [B(a)P]-induced lung carcinogenesis was investigated in Swiss albino mice. Lung cancer was induced by 50mg/kg body weight of B(a)P, given orally twice a week for 4 successive weeks in male Swiss albino mice. B(a)P-induced mice were pre- and post-treated with 12mg/kg body weight of BE, given orally once in a week for 16 weeks. After the experimental period, protein carbonyl content, total iron levels, reactive oxygen species (ROS) generation, DNA unwinding, levels of thiobarbituric acid reactive substances (TBARS), hydro-peroxides (OH) and glycoproteins (hexose, hexosamine and sialic acid) were found to be increased in the lung of B(a)P-induced mice. Accompanied by the activities of enzymic antioxidants [superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR) and glutathione-S-transferase (GST)], non-enzymic antioxidants (reduced glutathione, vitamin C, vitamin E and vitamin A), membrane bound ATPases (Na+/K+ ATPase, Mg2+ ATPase and Ca2+ ATPase) were found to be decreased due to induction of lung cancer in mice. Treatment (pre- and post-) with BE significantly ameliorated all these above alterations. The chemopreventive action observed in the present study is attributed to the antioxidant potential and free radical scavenging properties of BE against lung carcinogenesis in Swiss albino mice.

Antiproliferative and antioxidant potential of beta-ionone against benzo(a)pyrene-induced lung carcinogenesis in Swiss albino mice

Nowadays, in developing countries like India, incidence of lung cancer is increasing rapidly, and as a consequence it has become the most common cause of malignancy-associated death. This study is aimed to evaluate the therapeutic efficacy of beta-ionone (ION), a precursor for carotenoids against benzo(a)pyrene [B(a)P]-induced lung carcinogenesis. B(a)P (50 mg/kg body weight, orally twice a week for 4 successive weeks)-induced lung cancer in mice was assessed both in tissue and serum in terms of increase LPO and tissue marker enzymes, such as aryl hydrocarbon hydroxylase, γ-glutamyl transpeptidase, 5'-nucleotidase, and lactate dehydrogenase, and serum tumor markers such as carcinoembryonic antigen and neuron-specific enolase with concordant decrease in activities of tissue enzymic and non-enzymic antioxidants were observed on the treatment of ION (60 mg/kg body weight, orally twice a week for 16 weeks) significantly attenuated LPO and restored all cancer marker enzymes and antioxidants levels to near normal, which indicates the anticancer effect of ION. This was further confirmed by histological staining of argyrophilic nucleolar organizer region and histopathological analysis of lung tissue, immunohistochemical and immunoblot analysis of proliferating cell nuclear antigen. Overall findings suggested that the ION effectively ameliorated the lung carcinogenesis, which is attributed to the antiproliferative and antioxidant potential through free radical scavenging property.

Estrogen promotes benzo[a]pyrene-induced lung carcinogenesis through oxidative stress damage and cytochrome c-mediated caspase-3 activation pathways in female mice

Estrogen may contribute to the development of smoking-induced lung cancer in women. To test this hypothesis, an mouse model was used to investigate the effects of 17 beta-estradiol (E2) on benzo[a]pyrene (B[a]P)-induced lung carcinogenesis. We found that B[a]P could cause oxidative stress damage, upregulate mitochondrial cytochrome-c and caspase-3 expression, induce lung carcinogenesis in female mice, E2 promoted these effects of B[a]P while tamoxifen (TAM) inhibited this effects of E2. We conclude that E2 can promote the tumorigenic effects of B[a]P in female mice, and oxidative stress damage and activation of cytochrome-c-mediated caspase-3 pathway may be involved in this process.

Fisetin, a novel flavonol attenuates benzo(a)pyrene-induced lung carcinogenesis in Swiss albino mice

Lung cancer is the foremost cause of cancer mortality and is a growing economic burden worldwide. Fisetin (3,7,3′,4′-tetrahydroxyflavone), a naturally occurring flavonoid is found in vegetables and fruits possesses anti-oxidative, anti-inflammatory and anti-proliferative effects in a wide variety of cancer. In the present study it is hypothesized that fisetin may provide chemopreventive as well as chemotherapeutic effects against experimental lung carcinogenesis. The present study was designed to investigate whether fisetin confers anti-cancer action against benzo(a)pyrene [B(a)P] induced lung carcinogenesis. Treatment with fisetin significantly reduced the degree of histological lesions, restored the levels of lipid peroxidation (LPO), enzymic and non-enzymic anti-oxidants in B(a)P-induced mice. Anti-proliferative efficacy of fisetin was assessed by immunohistochemical analysis of proliferating cell nuclear antigen (PCNA) in B(a)P induced mice showed increased PCNA expression which is restored upon fisetin administration. Together, our results depicts that fisetin can be used as chemopreventive agent against lung cancer.

Hesperidin attenuates mitochondrial dysfunction during benzo(a)pyrene-induced lung carcinogenesis in mice

The present study is designed to assess the mitochondrial status during benzo(a)pyrene (B(a)P)-induced lung carcinogenesis in Swiss albino mice and to reveal the modulatory effect of hesperidin over it. B(a)P (50 mg/kg body weight)-induced mitochondrial abnormalities was evident from alterations in mitochondrial lipid peroxides, antioxidant status (superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, glutathione-S-transferase, reduced glutathione, vitamin E, and vitamin C), major tricarboxylic acid (TCA) cycle enzyme activities (isocitrate dehydrogenase, succinate dehydrogenase, malate dehydrogenase, alpha-ketoglutarate dehydrogenase), electron transport chain (ETC) complexes activities and ATP levels. Ultrastructural changes in lung mitochondria were also in accord with the above aberrations. Hesperidin (25 mg/kg body weight) supplementation effectively counteracted all the above changes and restored cellular normalcy, indicating its protective role during B(a)P-induced lung cancer.

Rehabilating Activity of Mangiferin in Benzo(a) Pyrene Induced Lung Carcinogenesis*

Rehabilating Activity of Mangiferin in Benzo(a) Pyrene Induced Lung Carcinogenesis*

An insight into the chemopreventive role of curcumin and quercetin during promotional phase of benzo(a)pyrene-induced lung carcinogenesis in mice

The aim of the present study was to gain insight into the combined chemopreventive potential of curcumin and quercetin during promotional phase of lung carcinogenesis in male Laka mice. The mice were segregated into five groups; normal control, benzo(a)pyrene (BP) treated, BP + curcumin treated, BP + quercetin treated, and BP + curcumin + quercetin treated. After 10 weeks of BP treatment a significant increase in lipid peroxidation (LPO) levels, a significant decrease in the glutathione (GSH) levels, as well as in the activities of superoxide dismutase (SOD) and well-differentiated histological signs of promotional phase were noted. Treatment with curcumin and quercetin when given separately as well as in combination restored LPO levels to within normal range. Quercetin alone supplementation and in combination with curcumin significantly elevated the levels of GSH as well as the activities of SOD in the BP-treated mice. Further, treatment with quercetin and curcumin given separately, as well as in combination, to the BP-treated mice showed protective effects in the lung morphology. In conclusion, results suggest that treatment with curcumin and quercetin alone and in combination provides beneficial effects against BP-induced lung alterations in mice.

Antioxidant and anticancer efficacy of hesperidin in benzo(a)pyrene induced lung carcinogenesis in mice

Chemoprevention is regarded as one of the most promising and realistic approaches in the prevention of cancer. Several bioactive compounds present in fruits and vegetables have revealed their cancer curative potential on lung cancer. Hesperidin is one such naturally occurring flavonoid widely found in citrus fruits. The aim of the present study is to divulge the chemopreventive nature of hesperidin during benzo(a)pyrene (B(a)P) induced lung cancer in Swiss albino mice. Administration of B(a)P (50 mg/kg body weight) to mice resulted in increased lipid peroxides (LPO), lung specific tumor marker carcinoembryonic antigen (CEA) and serum marker enzymes aryl hydrocarbon hydroxylase (AHH), gamma glutamyl transpeptidase (GGT), 5'nucleotidase (5'ND) and lactate dehydrogenase (LDH) with concomitant decrease in the levels of tissue antioxidants like superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), reduced glutathione (GSH), vitamin E and vitamin C. Hesperidin supplementation (25 mg/kg body weight) significantly attenuated these alterations thereby showing potent anticancer effect in lung cancer. Further the antiproliferative effect of hesperidin was confirmed by histopathological analysis and proliferating cell nuclear antigen (PCNA) immunostaining. Overall, these findings substantiate the chemopreventive potential of hesperidin against chemically induced lung cancer in mice.

Tea polyphenols can restrict benzo[ a]pyrene-induced lung carcinogenesis by altered expression of p53-associated genes and H-ras, c-myc and cyclin D1

The modulatory influence of tea polyphenols (epigallocatechin gallate, epicatechin gallate and theaflavin) on benzo[ a]pyrene (B[ a]P)-induced lung carcinogenesis in mice was analyzed using histopathological and molecular parameters. Progression of lung lesions was restricted at the hyperplastic stage by tea polyphenols. A significant reduction in cellular proliferative index and an increase in apoptotic index were noted in the restricted lung lesions. High expression of H-ras, c-myc, cyclin D1 and p53 genes was seen at the inflammatory stage (9th week) and in subsequent premalignant lesions, but down-regulation of H-ras at the hyperplastic stage (17th week). Expression of bcl-2 was high in hyperplastic lesions, whereas the expression of mdm2 and bcl-xl increased only at the moderately dysplastic stage (36th week). The tea polyphenols inhibited inflammatory response in the lung lesions on the 9th week, when decreased expression of H-ras and c-myc and increased expression of bax were noted. Prolonged treatment (>9th week) with tea polyphenols resulted in changes in the expression of some additional genes, such as reduced expression of cyclin D1 (from the 17th week), bcl-2 (from the 26th week; mild dysplasia) and p21 (on the 36th week), and high expression of p53 (from the 17th week) and p27 (on the 36th week). These observations indicate that the tea polyphenols can restrict B[ a]P-induced lung carcinogenesis by differential modulation of the expression of p53 and its associated genes such as bax, bcl-2, mdm2, p21 and p27, along with H-ras, c-myc and cyclin D1, at different time points.

Cytoprotective Effect of Mangiferin on Benzo(a)pyrene‐Induced Lung Carcinogenesis in Swiss Albino Mice

Antioxidants are one of the key players in tumourigenesis, and several natural and synthetic antioxidants have been shown to have anticancer effects. In the present investigation, the efficacy of mangiferin on the antioxidant status of benzo(a)pyrene-induced lung carcinogenesis in Swiss albino mice was assessed. The animals were divided into five groups. The animals in groups I and V were normal control and mangiferin control, respectively. Groups II, III and IV were administered with benzo(a)pyrene (50 mg/kg body weight, orally) for 4 weeks (twice a week) to induced lung carcinogenesis. Starting 1 week prior to benzo(a)pyrene administration, group III animals were treated with mangiferin (100 mg/kg body weight) in the diet for 18 weeks; 12 weeks after benzo(a)pyrene administration, group III animals were treated with mangiferin that continued until the end of the experiment period (18 weeks). At the end of the experiment period, the reactive oxygen species, glutathione and the activities of antioxidant enzymes were assessed in both lung and liver tissues. The levels of glutathione, superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, vitamin E and vitamin C were decreased in group II animals. However, in the mangiferin + benzo(a)pyrene-treated groups III and IV, the levels of GSH and the activities of antioxidant enzymes in both lung and liver were improved when compared with benzo(a)pyrene-induced group II animals. In addition, the finding that mangiferin decreased reactive oxygen species levels and enhanced antioxidant status suggests that this polyphenol might also be of value in the prevention of benzo(a)pyrene-induced lung carcinogenesis.

Chemopreventive efficacy of mangiferin against benzo( a)pyrene induced lung carcinogenesis in experimental animals

Chemoprevention has emerged as a very effective preventive measure against carcinogenesis. Several bioactive compounds present in fruits and vegetables have revealed their cancer curative potential on carcinogenesis. Tumor markers correlate strongly with prognosis on tumor burden. Glycoprotein and membrane ATPases play an important role in carcinogenesis. Hence this study was launched to evaluate the effect of mangiferin on the changes in glycoprotein components, ATPases and membrane lipid peroxidation in control and lung carcinoma bearing mice. A significant increase in the levels of glycoproteins, membrane ATPases and membrane lipid peroxidation were observed in animals with lung carcinoma. On administration of mangiferin, these changes were reverted back to near normal levels. The increased levels of glycoprotein components found in lung carcinoma were also significantly decreased in mangiferin treated. Overall, the above data shows that the anticancer effect of mangiferin is more pronounced when used as an chemopreventive agent rather than as a chemotherapeutic agent against B( a)P induced lung carcinogenesis.