Showing papers on "7,12-Dimethylbenz[a]anthracene published in 2016"
TL;DR: The data obtained from the study indicate that Pleurotus ostreatus ethanolic extract at a dose of 600 mg/kg bwt possesses optimum anticancer effects against DMBA induced mammary carcinogenesis, which concludes that the POEet is having a potent antioxidant capacity.
Abstract: Background: Worldwide, breast cancer is the second most prevalent cancer among women and its incidence is increasing alarmingly. Aim: To determine a dose-response effect of Pleurotus ostreatus on oxidant/antioxidant status in 7,12-dimethylbenz. (a) antheracene induced. (DMBA) mammary carcinoma in experimental rats. Materials and Methods: Cancer bearing female Sprague Dawley rats were orally treated with Pleurotus ostreatus ethanolic extract (POEet) (150, 300 and 600 mg/kg body weight) for 16 weeks. By means of high performance liquid chromatography (HPLC) analysis, ergosterol (48.82%) were identified and quantified in POEet. Body weight of experimental rats in each groups and the biochemical parameters of plasma, liver and mammary tissues were carried out. Histopathological analyses were also determined. Statistical Analysis Used: Results were analyzed using SPSS software package, version 16.0. The values were analyzed by one way analysis of variance (ANOVA) followed by Duncan's multiple range test (DMRT). Result: The result showed that depleted activities of enzymatic and non-enzymatic antioxidant level and significant elevated TBARS level were observed in DMBA group of plasma, mammary and liver tissues of experimental rats. The effects were dose.dependent and the above noted parameters were renovated to near normal after supplementation with different dose of POEet (150 mg, 300 mg and 600 mg/kg bwt). The data obtained from the study indicate that POEet at a dose of 600 mg/kg bwt possesses optimum anticancer effects against DMBA induced mammary carcinogenesis. Conclusion: Based on the scientific appraisal, we conclude that the POEet is having a potent antioxidant capacity; thereby it offers maximum protection against DMBA-induced mammary carcinogenesis
40 citations
TL;DR: DAP inhibits mammary carcinogenesis through multiple mechanisms and dual efficacy of DAP on Nrf-2-Keap1 pathway and NF-κB expressions propose it as a potential chemotherapeutic agent in mammary cancer management.
33 citations
TL;DR: It is concluded that shogaol prevents DMBA‐induced HBP carcinogenesis through its antioxidant as well as modulating apoptotic signals.
Abstract: Oral cancer is a major cause of morbidity and mortality in developing countries. Despite advances in chemotherapy for the cancer management, the survival rate has not yet been improved. Dietary nutrient has been receiving a lot of attention and interest in the chemotherapeutic development. [6]-Shogaol is a major bioactive compound identified in ginger that possesses many pharmacological properties. The aim of the present study is to investigate the effect of [6]-shogaol on 7,12-dimethylbenz[a]anthracene-induced hamster buccal pouch (HBP) carcinogenesis. Oral squamous cell carcinoma induced in HBP by painting with 0.5% 7,12-dimethylbenz(a)anthracene (DMBA), thrice in a week for 16 weeks. We observed 100% tumour incidence, decreased levels of lipid peroxidation, antioxidant, and phase II detoxification enzymes (GST, GR and GSH) in DMBA-induced hamsters. Further, enhanced activity of phase I enzymes (cytochrome p450 and b5) and over-expression of mutant p53, Bcl-2 and decreased expression of wild type p53 and Bax were noticed in DMBA-induced hamsters. Our results indicated that [6]-shogaol (10, 20 and 40 mg/kg body weight) treated with DMBA-painted hamsters, considerably reversed tumour incidence, improved antioxidant status, phase II detoxification enzymes, and also inhibit lipid peroxidation and phase I enzymes. Moreover, [6]-shogaol inhibits mutant p53 and Bcl-2 expression and significantly restored normal p53, Bax levels. Thus, we concluded that [6]-shogaol prevents DMBA-induced HBP carcinogenesis through its antioxidant as well as modulating apoptotic signals.
28 citations
TL;DR: Blueberry supplementation inhibited the development and progression of HBP carcinomas by abrogating TGF-β and PI3K/Akt pathways and inhibited angiogenesis in ECV304 cells by suppressing migration and tube formation, suggesting that targeting oncogenic signaling pathways that influence acquisition of cancer hallmarks is an effective strategy for chemointervention.
Abstract: Aberrant activation of oncogenic signaling pathways plays a pivotal role in tumor initiation and progression. The purpose of the present study was to investigate the chemopreventive and therapeutic efficacy of blueberry in the hamster buccal pouch (HBP) carcinogenesis model based on its ability to target TGF-β, PI3K/Akt, MAPK and NF-κB signaling and its impact on invasion and angiogenesis. Squamous cell carcinomas were induced in the HBP by 7,12-dimethylbenz[a]anthracene (DMBA). The effect of blueberry on the oncogenic signaling pathways and downstream events was analyzed by quantitative real-time PCR and immunoblotting. Experiments with the ECV304 cell line were performed to explore the mechanism by which blueberry regulates angiogenesis. Blueberry supplementation inhibited the development and progression of HBP carcinomas by abrogating TGF-β and PI3K/Akt pathways. Although blueberry failed to influence MAPK, it suppressed NF-κB activation by preventing nuclear translocation of NF-κB p65. Blueberry also modulated the expression of the oncomiR miR-21 and the tumor suppressor let-7. Collectively, these changes induced a shift to an anti-invasive and anti-angiogenic phenotype as evidenced by downregulating matrix metalloproteinases and vascular endothelial growth factor. Blueberry also inhibited angiogenesis in ECV304 cells by suppressing migration and tube formation. The results of the present study suggest that targeting oncogenic signaling pathways that influence acquisition of cancer hallmarks is an effective strategy for chemointervention. Identification of modulatory effects on phosphorylation, intracellular localization of oncogenic transcription factors and microRNAs unraveled by the present study as key mechanisms of action of blueberry is critical from a therapeutic perspective.
25 citations
TL;DR: Paternal selenium deficiency increased the number of terminal end buds, epithelial elongation and cell proliferation in the mammary gland of the female rat offspring and these effects were associated with higher susceptibility to DMBA‐induced mammary tumors, while supplementation did not influence any of these parameters.
Abstract: Breast cancer is a global public health problem and accumulating evidence indicates early-life exposures as relevant factors in the disease risk determination. Recent studies have shown that paternal nutrition can influence offspring health including breast cancer risk. Selenium is a micronutrient with essential role in central aspects of embryogenesis, male fertility and cancer and that has been extensively studied as a chemopreventive agent in several breast cancer experimental models. Thus, we designed an animal study to evaluate whether paternal selenium deficiency or supplementation during preconception could affect the female offspring mammary gland development and breast cancer susceptibility. Male Sprague-Dawley rats were fed AIN93-G diet containing 0.15 ppm (control diet), 0.05 ppm (deficient diet) or 1 ppm (supplemented diet) of selenium for 9 weeks and mated with control female rats. Mammary carcinogenesis was induced with 7,12-dimethylbenz[a]anthracene (DMBA) in their female offspring. Paternal selenium deficiency increased the number of terminal end buds, epithelial elongation and cell proliferation in the mammary gland of the female rat offspring and these effects were associated with higher susceptibility to DMBA-induced mammary tumors (increased incidence and higher grade tumors). On the other hand, paternal selenium supplementation did not influence any of these parameters. These results highlight the importance of father's nutrition including selenium status as a relevant factor affecting daughter's breast cancer risk and paternal preconception as a potential developmental stage to start disease preventive strategies.
19 citations
TL;DR: It is suggested that luteolin possesses anti-angiogenic properties which could mechanistically explain its capacity to control tumor progression, and may be a valuable, non-toxic, naturally-occurring anticancer compound which may potentially be used to combat progestin-accelerated mammary tumors.
Abstract: Postmenopausal women undergoing hormone-replacement therapy containing both progestins and estrogens are at an increased risk of developing breast cancer compared with women taking estrogen alone. We recently demonstrated that medroxyprogesterone acetate, a progestin commonly used for hormone-replacement therapy, accelerates development of mammary carcinogenesis in 7,12-dimethylbenz(a)anthracene‑treated Sprague-Dawley rats. Synthetic antiprogestins used to block the deleterious effects of progestins, are themselves associated with toxic side-effects. In order to circumvent this, we used the aforementioned model to identify less toxic natural compounds that may prevent the development of progestin-accelerated tumors. Luteolin, a naturally-occurring flavonoid commonly found in fruits and vegetables, has previously been shown to possess anticancer properties. In our studies, both low (1 mg/kg) and high (25 mg/kg) doses of luteolin significantly suppressed progestin-dependent increases in tumor incidence, while increasing tumor latency and reducing the occurrence of large (>300 mm3) mammary tumors. However, an intermediate dose of luteolin (10 mg/kg), while suppressing the development of large tumors, did not affect either tumor incidence or latency. Immunohistochemical analysis of tumor tissues revealed that all concentrations of luteolin (1, 10, and 25 mg/kg) significantly reduced levels of VEGF within tumors. The suppressive effects of luteolin on tumor incidence and volume, together with its ability to reduce VEGF and blood vessels, persisted even after treatment was terminated. This suggests that luteolin possesses anti‑angiogenic properties which could mechanistically explain its capacity to control tumor progression. Thus luteolin may be a valuable, non-toxic, naturally-occurring anticancer compound which may potentially be used to combat progestin-accelerated mammary tumors.
19 citations
TL;DR: Vitamin D3 can delay the progression of ovarian cancer induced by DMBA, and the administration of vitamin D3 during the whole process worked more effectively than the administration only during tumor initiation or promotion.
Abstract: Purpose
Ovarian cancer is the most lethal malignancy of the female reproductive system, and the prevention and treatment of ovarian carcinoma are still far from optimal. Epidemiological studies reported that ovarian cancer risk was inversely associated with low level of 25-hydroxy vitamin D [25(OH)]. Therefore, this study focuses on exploring the chemoprevention of vitamin D on epithelial ovarian cancer induced by 7, 12-dimethylbenz [a] anthracene (DMBA).
18 citations
TL;DR: Investigation of the effect of dietary Diosmin on IL-6/STAT-3 signaling in the 7,12-dimethylbenz[a]anthracene (DMBA)-induced hamster buccal pouch carcinogenesis provides significant evidence that Diosmine prevents the development and progression of HBP carcinomas through the inhibition of IL- 6/STAT -3 signaling and its downstream events.
18 citations
TL;DR: Silymarin NLC possessed activities against progression and proliferation, which were associated with enhanced solubility and stability of sily marin and greater permeation into the affected cells, which could therefore be useful for chemo preventive use in skin cancer, as a topical formulation.
Abstract: Stable and novel silymarin bearing nanostructured lipid carriers (NLC) were prepared using a hot high pressure homogenization process. Silymarin NLC were physicochemically characterized via particle size, zeta potential, transmission electron microscope (TEM), entrapment efficiency (EE), in vitro release studies and optimized through experimental design. Stability data confirmed a stable dosage form. The anti proliferative activity of silymarin NLC was studied in 7,12-dimethylbenz[a]anthracene (DMBA) induced cellular progression/differentiation in an albino mice model using western blot and reverse transcription polymerase chain reaction (RT-PCR) analysis. In order to see the molecular changes with cellular proliferative controls such asornithine decarboxylase (ODC), proliferating cell nuclear antigen (PCNA), cyclooxygenase-2 (COX-2) and cyclin D1 at protein and messenger ribonucleic acid (mRNA) level were studied. The proliferation markers such as ODC, COX-2, cyclin D1 displayed reduced levels. In conclusion, silymarin NLC possessed activities against progression and proliferation, which were associated with enhanced solubility and stability of silymarin and greater permeation into the affected cells. Silymarin NLC could therefore be useful for chemo preventive use in skin cancer, as a topical formulation.
15 citations
TL;DR: Fatty acids profile was the result of prolonged exposure to high dose of CLA and DMBA administration and underlined the differences in fatty acids profiles among clusters of animals.
Abstract: We investigated how different doses of conjugated linoleic acids applied for various periods of time influence breast cancer risk and fatty acids profile in serum of rats treated or not with 7,12-dimethylbenz[a]anthracene (DMBA). We also search for interactions among parameters describing health conditions and cancer risk. Animals were divided into 18 groups with different diet modifications (vegetable oil, 1.0%, 2.0% additions of CLA) and different periods of supplementation. In groups treated with DMBA mammary adenocarcinomas appeared. Due to the complexity of experiment apart from statistical analysis a chemometric tool-Partial Least Square method was applied. Analysis of pairs of correlated parameters allowed to identify some regularities concerning the relationships between fatty acid profiles and clinical features of animals. Fatty acids profile was the result of prolonged exposure to high dose of CLA and DMBA administration. These two factors underlined the differences in fatty acids profiles among clusters of animals.
12 citations
TL;DR: The data suggest that VEGF-D may be beneficial in early-stage tumors since it suppresses the pro-tumorigenic inflammation, while at later stages VEGf-D-induced tumor lymphatics provide a route for metastasis.
TL;DR: Evaluation of DNA repair in DMBA-treated BMCs, indicated long-lasting genotoxicity and cytotoxicity in BMC from AIRmin mice and a blockade of cell cycle progression.
TL;DR: This response increased constitutively in Cyp1b1‐ko BM, demonstrating that CYP1B1 metabolizes local stimulants that impact a basal progenitor protection process and is associated with elevated chemokines and cytokines that depend on AhR‐mediated induction of CYP 1A1.
Abstract: Bone marrow (BM) hematopoietic stem cells differentiate to common lymphoid progenitors (CLP) that emigrate to the thymus to form T cells or differentiate into immature B cells that then migrate to the spleen for maturation. Rapid in vivo suppression of BM progenitor cells by a single oral or intraperitoneal dose of 7,12-dimethylbenz(a)anthracene (DMBA) subsequently decreased mature lymphoid populations in BM, spleen, and thymus. These suppressions depended on BM CYP1B1, but not on aryl hydrocarbon receptor (AhR) activity. Suppression of pre-B colony formation at 6 h, correlated with subsequent decreases in mature BM, spleen, and thymus populations (48-168 h). Thymus T-cell ratios were unaffected, suggesting low local toxicity. DMBA treatment suppressed progenitor cells 24-h post treatment in wild type (WT), AhRb mice, but not in Cyp1b1-ko mice. The stem cell populations were sustained. Benzo(a)pyrene (BP) mediated a similar progenitor suppression up to 6 h, but reversal rapidly ensued. This recovery was absent in mice with a polycyclic aromatic hydrocarbon (PAH)-resistant, AhRd genotype. This AhR-dependent progenitor recovery with BP induction accounts for the absence of suppression of B220+ BM and spleen populations at 48-168 h. However, DMBA and BP produced similar profiles for thymus cell suppression, independent of AhR genotype. Thus, lymphoid progenitors may exit the BM to the thymus prior to the BP reversal. This progenitor recovery is associated with elevated chemokines and cytokines that depend on AhR-mediated induction of CYP1A1. This response increased constitutively in Cyp1b1-ko BM, demonstrating that CYP1B1 metabolizes local stimulants that impact a basal progenitor protection process.
TL;DR: The results suggested that toona sinensis leaf extract might be a promising candidate for the prevention of oral cancer.
TL;DR: It is demonstrated that tangeretin specifically regulates cellular metabolic energy fluxes in DMBA-induced breast cancer-bearing rats.
TL;DR: The nano formulation of DIM with chitosan provides a novel therapeutic regime for mammary cancer and is concluded one of the best chemotherapeutic potential for various malignancies.
TL;DR: This report shows that DMBA (7,12-dimethylbenz[a]anthracene), a chemical carcinogen, induces mammary tumor formation at a significantly higher frequency in the Smad3 heterozygous mice than in theSmad3 wild type mice.
Abstract: Previous studies based on cell culture and xenograft animal models suggest that Smad3 has tumor suppressor function for breast cancer during early stages of tumorigenesis. In this report, we show that DMBA (7,12-dimethylbenz[a]anthracene), a chemical carcinogen, induces mammary tumor formation at a significantly higher frequency in the Smad3 heterozygous mice than in the Smad3 wild type mice. This is the first genetic evidence showing that Smad3 inhibits mammary tumor formation in a mouse model. Our findings support the notion that Smad3 has important tumor suppressor function for breast cancer.
TL;DR: Taurine treatment appreciably counteracted all the above changes induced by DMBA and clearly demonstrated the chemotherapeutic effect of taurine in DMBA‐induced breast cancer.
Abstract: The modulatory effect of taurine on 7,12-dimethylbenz(a)anthracene (DMBA)-induced breast cancer in rats was studied. DMBA (25 mg/kg body weight) was administered to induce breast cancer in rats. Protein carbonyl levels, activities of membrane bound enzymes (Na(+) /K(+) ATPase, Ca(2+) ATPase, and Mg(2+) ATPase), phase I drug metabolizing enzymes (cytochrome P450, cytochrome b5, NADPH cytochrome c reductase), phase II drug metabolizing enzymes (glutathione-S-transferase and UDP-glucuronyl transferase), glycoprotein levels, and proliferative cell nuclear antigen (PCNA) were studied. DMBA-induced breast tumor bearing rats showed abnormal alterations in the levels of protein carbonyls, activities of membrane bound enzymes, drug metabolizing enzymes, glycoprotein levels, and PCNA protein expression levels. Taurine treatment (100 mg/kg body weight) appreciably counteracted all the above changes induced by DMBA. Histological examination of breast tissue further supported our biochemical findings. The results of the present study clearly demonstrated the chemotherapeutic effect of taurine in DMBA-induced breast cancer.
Journal Article•
01 Jan 2016
TL;DR: Experimental evidence is provided that leaves of mulberry may have chemopreventive effects on cancerous growth and ethanolic extractive of Mulberry leaves was found preventing significantly the incidence, volume and burden of the buccal pouch carcinoma.
Abstract: The leaf extract of mulberry, Morus alba (L) in ethanol was used to treat the 7,12dimethylbenz-anthracene (DMBA) induced carcinoma in the buccal pouch of Syrian hamster, Mesocricetus auratus (L). The 0.5 percent DMBA in liquid paraffin was used for painting the buccal pouch. The DMBA treatment was carried thrice a week for 14 weeks. This was resulted into squamous cell carcinoma. The parameters analyzed include: The tumor incidence, volume and burden. It was followed by oral treatment with ethanolic extractives of mulberry leaves (TpEt) at a dosage of 300 mg/kg, body weight, to DMBA (on alternate days for 14 weeks)painted animals. Administration of ethanolic extractive of mulberry leaves was found preventing significantly the incidence, volume and burden of the buccal pouch carcinoma. The ethanolic extractive of mulberry leaves exhibited significant effect, especially, the antilipidperoxidation and antioxidative enhancement in DMBA individuals of Syrian hamsters. The results are demonstrating the potency of ethanolic extractive of mulberry leaves for chemoprevention and significant antilipidperoxidative influence in 7,12dimethylbenz-anthracene (DMBA)induced carcinoma in the buccal pouch of Syrian hamster, Mesocricetus auratus (L). The activation of caspase through release of cytochrome C through disruption of mitochondrial membrane potential may be the sequence of action of the active principles of mulberry leaf extractives. With it’s bioactive compounds, mulberry, Morus alba (L) may open a World Scientific News 30 (2016) 1-13 -2new avenue in the cancer prevention and treatment. Taken together, the present attempt provide experimental evidence that leaves of mulberry may have chemopreventive effects on cancerous growth. Mulberry, Morus alba (L) may provide a therapeutic option for controlling the growth of cancer cells.
TL;DR: It is demonstrated that ethanolic extract leaves of G. procumbens in 300 mg/kg BW dose could inhibit CYP1A1 stronger than are other and induced GST* level, which should be taken into account for chemopreventing agent in mammary carsinogenesis.
Abstract: The cytochrome P-450 (CYP) and glutathione S-transferase (GST) enzyme systems may influence the biological effects of carcinogens. As such, these enzymes may predict the developmental risk of breast cancer, as well as be potential targets for chemoprevention. The purpose of this study was to compare the expression of CYP1A1 and GST* between treatment groups. Expression of CYP1A1 and GST* was quantified in liver tissue from 18 female Sprague Dawley rats aged 40 days, which randomly divided into six treatment groups. Those are base line group (without DMBA and ethanolic extract treatment), DMBA induced cancer group, the other two groups was administrated by DMBA after treated by ethanolic extract in two different doses, 300 mg /kg BW and 750 mg/kg BW. The last two groups were given two doses of extract ethanolic only, without initiated of DMBA. The ingestion of the extract was carried for three weeks and the ingestion of DMBA was performed twice in the third week. The expression CYP1A1 and GST was quantified by immunohistochemistry. CYP1A1 expression was significantly higher (P < 0.05) in cancer group (DMBA) as compared with other groups. On the other hand, GST expression was lower in cancer group (P < 0.05). Result of this study demonstrated that ethanolic extract leaves of G. procumbens in 300 mg/kg BW dose could inhibit CYP1A1 stronger than are other and induced GST* level. Has effect on ethanolic extract leaves of G. procumbens has ability in played role of as blocking agent in preventing initiation stage of carsinogenesis, therefore it should be taken into account for chemopreventing agent in mammary carsinogenesis. Key words : Gynura procumbens, breast cancer, Chemopreventive, CYP1A1, GSTμ
Journal Article•
TL;DR: The apoptotic and anti-cell proliferative efficacy of cromolyn might have suppressed DMBA induced tumorgenesis in the buccal pouches of golden Syrian hamsters.
Abstract: The present study evaluated the effect of cromolyn on the expression pattern of genes involved in the process of apoptosis (P 53 , Bcl-2, Bax, Bcl-xL and Bad) and cell proliferation (PCNA, Cyclin D1, CDK4, CDK6 and Survivin) during 7,12-dimethylbenz(a)anthracene (DMBA)induced hamster buccal pouch carcinogenesis. Hamsters buccal pouches exposed to 0.5% DMBA in liquid paraffin, three times a week for 14 weeks, developed well differentiated squamous cell carcinoma. Administration of cromolyn at a dose of 80mg/kg b.w orally to hamsters treated with DMBA not only prevented the tumor formation but also induced apoptosis and suppressed cell proliferation. Thus, the apoptotic and anti-cell proliferative efficacy of cromolyn might have suppressed DMBA induced tumorgenesis in the buccal pouches of golden Syrian hamsters.
TL;DR: Collectively, the enhanced chemopreventive potential of natural compound in combination via regulation of K-Ras-PI3K-AKTpathway along with regulatory micro RNAs provide a newer and effective mean for cancer management.
TL;DR: The dietary consumption of P. ostreatus might offer maximum protection against DMBA-induced mammary carcinogenesis and improving human health if used as a regular basis, based on scientific appraisal.
Journal Article•
TL;DR: Lfcin B may act as a promising chemoprotective agent against DMBA induced skin cancer through acting as an antioxidant, thereby inhibiting carcinogenesis, hepatocellular and renal damage.
Abstract: Objective: To investigate the chemo-preventive effect of subcutaneous injection of bovine lactofericin (LfcinB) against 7, 12 dimethylbenz (a) anthracene (DMBA) induced carcinogenesis in swiss albino female mice. Methods: 30 animals were divided into 3 groups. 200μl of DMBA (0.025μg/μl) per animal three times per week as topical was used to induce skin cancer in both groups II and III. In addition to DMBA, group III was protected with subcutaneous injection of LfcinB (20μg/μl) while group I served as control. At the end of 16 th week lysates/blood/serum were subjected to various tests such as antioxidant, glucose, liver enzymes and kidney marker parameters. Results: Topical application of 200μl DMBA (0.025μg/μl) per animal three times per week has produced 100% tumor incidence in DMBA treated group at the end of 16 th week whereas only 20% developed tumors in the LfcinB+DMBA treated group. Antioxidants level were found to be significantly (P<0.01) depleted in reduced glutathione (GSH), glutathione reductase (GR), glutathione peroxidase (GPx), catalase (CAT) and liver enzymes, Alaninine aminotransferase (ALT) and Alkaline phosphatase (ALP). Subcutaneous administration of 200μl of LfcinB (20μg/μl) significantly (P<0.01) normalized the antioxidants (GSH, GR, GPx and CAT) levels. Conclusion: LfcinB exerts its chemoprotective effect through acting as an antioxidant, thereby inhibiting carcinogenesis, hepatocellular and renal damage. Lfcin B may act as a promising chemoprotective agent against DMBA induced skin cancer.
Journal Article•
TL;DR: The results of the present study clearly indicate that TQ protects the tissues from oxidative stress-mediated damage which is evident from improved antioxidant status.
Abstract: Objective: Thymoquinone (TQ), the main active ingredient of the volatile oil isolated from the Nigella sativa seeds has been shown to possess a wide array of pharmacological effects. Recently, we have reported the anticancer potential of TQ in 7, 12-dimethylbenz (a) anthracene (DMBA) induced rats. DMBA acts as a potent site and organ-specific carcinogen by generating various reactive metabolic intermediates leading to oxidative stress. The present study was hypothesized to explore the protective effect of TQ against DMBA induced liver injury in rats. Methods: DMBA was used to induce breast cancer in rats. Oral treatment of TQ (25 mg/kg body weight) to DMBA induced rats daily for 4 weeks was found to be effective against DMBA induced mammary gland carcinogenesis in female Wistar rats. The levels of nucleic acids, oxidative stress mark and antioxidants were determined. The activities of Phase I and Phase II enzymes, tricarboxylic acid (TCA) cycle enzymes were assayed. Results: The increased levels of DNA and RNA were found to be decreased on treatment with TQ. The altered activities of Phase I and Phase II biotransformation enzymes were found to be regulated on treatment with thymoqionone. The hepatoprotective nature of TQ was assessed by analyzing the markers of oxidative stress, and antioxidant competence in DMBA induced rats. Treatment with TQ revealed a significant decline in the levels of lipid peroxides, and a significant improvement in the levels of enzymatic and non-enzymatic antioxidants in the liver tissue. In addition, TQ modulated the activities of TCA cycle enzymes. Conclusion: The results of the present study clearly indicate that TQ protects the tissues from oxidative stress-mediated damage which is evident from improved antioxidant status. Keywords: 7, 12-dimethylbenz (a) anthracene, Thymoquinone, Oxidative stress, Liver tissues, Antioxidant potential.
Journal Article•
TL;DR: It is suggested that glycyrrhetinic acid improved the status of lipid peroxidation and antioxidant defense mechanism during DMBA induced hamster buccal pouch carcinogenesis.
Abstract: Present study investigated the effect of glycyrrhetinic acid on lipid peroxidation and antioxidants status in 7,12-dimethylbenz(a)anthracene (DMBA) induced hamster buccal pouch carcinogenesis. Topical application of DMBA for 14 weeks in the buccal pouch of hamsters resulted in well-developed squamous cell carcinoma. The status of lipid peroxidation and antioxidants were measured in the plasma and buccal mucosa of hamsters treated with DMBA alone and DMBA + glycyrrhetinic acid treated hamsters. Altered levels of lipid peroxidation by-products [Thiobarbituric acid reactive substances (TBARS)] and disturbances in antioxidants status [vitamin E, reduced glutathione (GSH), superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx)] were noticed in hamsters treated with DMBA alone. Oral administration of glycyrrhetinic acid at a dose of 45 mg/kg b.w restored the status of lipid peroxidation and antioxidants in hamsters treated with DMBA. Present study thus suggests that glycyrrhetinic acid improved the status of lipid peroxidation and antioxidant defense mechanism during DMBA induced hamster buccal pouch carcinogenesis.
Journal Article•
TL;DR: In this paper, the chemopreventive potential of cromolyn against 7,12-dimethylbenz(a)anthracene (DMBA) induced oral carcinogenesis was investigated.
Abstract: Cromolyn explored diverse pharmacological effects including antioxidant, anti-inflammatory and anticancer properties. The cytotoxic or anti-cell proliferative potential of cromolyn has been well documented in various cancer cell lines. To date, there are no studies on the chemopreventive potential of cromolyn against 7,12-dimethylbenz(a)anthracene (DMBA) induced oral carcinogenesis. The chemopreventive efficacy of the cromolyn was substantied with the incidence of tumor formation, histological abnormalities and by analysing the status of biochemical markers such as lipid peroxidation by products, antioxidants and phase I and II detoxification agents in DMBA induced hamster buccal pouch carcinogenesis. Well differentiated squamous cell carcinoma was noticed in the buccal pouches of hamsters treated with DMBA (three times a week for 14 weeks). Cromolyn completely prevented the tumor formation and restored the status of biochemical markers in the pre-initiation phase. Also cromolyn reduced the tumor size and burden as well as improved the status of biochemical markers in the postinitiation phase. The present results thus implicate the tumor preventive potential of cromolyn in DMBA induced hamster buccal pouch carcinogenesis.
01 Jan 2016
TL;DR: The tumor preventive potential of cromolyn relies on its anti-inflammatory and anti-angiogenic potential in 7, 12-dimethylbenz(a)anthracene induced hamster buccal pouch carcinogenesis.
Abstract: Objectives: Cromolyn, a potent and safe anti-inflammatory drug, is used as a safe medication for the prophylactic treatment of asthma. The present study explores its anti-inflammatory and anti-angiogenic potential of cromolyn by analysing the expression pattern of inflammatory (NF-κB, COX-2, iNOS, IL-6 and IL-10) and angiogenic (VEGF) in 7, 12-dimethylbenz(a)anthracene (DMBA) induced hamster buccal pouch carcinogenesis. Methods: Topical application of 0.5% DMBA (three times a week) in the buccal pouches of hamsters resulted in well differentiated squamous cell carcinoma after 14 w. Results: While tumor formation was observed in all the hamsters treated with DMBA alone, we noticed only precancerous lesions such as hyperkeratosis, hyperplasia, and mild dysplasia in DMBA+cromolyn treated hamsters. Furthermore, cromolyn prevented the dysregulation induced by DMBA on the expression pattern of inflammatory and angiogenic markers. Conclusion: The present study thus concludes that the tumor preventive potential of cromolyn relies on its anti-inflammatory and anti-angiogenic potential in 7, 12-dimethylbenz(a)anthracene induced hamster buccal pouch carcinogenesis.
08 Aug 2016
TL;DR: The results clearly suggest that combination therapy of amla and cisplatin had inhibitory effect during oral carcinogenesis via induction of apoptosis and suppression of molecules involved in cell proliferation and angiogenesis.
Abstract: Amla fruit has been conventionally used as a health food for the prevention and therapy of cancer. Accordingly, the study aimed to explore the chemotherapeutic efficacy of amla and cisplatin combination on molecular mechanistic apoptosis implicated in proliferation, apoptosis and angiogenesis moleules during DMBA-induced buccal pouch carcinogenesis. Our western blot results showed that up regulation of Bcl-2, cyclin D1, Proliferating cell nuclear antigen, Cdc25C, Cox-2, Vascular endothelial growth factor and Survivin were observed in DMBA treated groups, whereas after treatment with combination therapy significantly down regulated the above noted proteins expression level. It was also observed that combination of amla and cisplatin treated tumor groups induced increased levels of Bax, caspase-3 and caspase-9 levels. More intriguingly, the effect was more pronounced in the tumor animals receiving combination therapy suggesting a synergistic effect. The results clearly suggest that combination therapy of amla and cisplatin had inhibitory effect during oral carcinogenesis via induction of apoptosis and suppression of molecules involved in cell proliferation and angiogenesis. Thus, amla fruit contains novel rich source of natural antioxidants and can be considered as an adjuvant therapeutic agent with cisplatin for oral cancer.