DMBA Group Research Articles

TOPICAL COCOA APPLICATION AS A PROTECTIVE AGENT AGAINST SKIN CANCER DUE TO THE EXPOSURE OF 7,12-DIMETHYLBENZEN (A) ANTHRACENE (DMBA) IN CORRELATION WITH MELONDYALDEHYDE (MDA), AND EXPRESSION OF BCL 2

Introduction : Skin cancer is one type of cancer which the number of the patient increases from year to year. Cocoa has powerful antioxidant content, such as flavonoids, catechins, epicathechin and proanthocyanidin which in a previous study showed protective effects against cancer. Carcinogenic agents induce the release of reactive oxygen species (ROS), which damage DNA, RNA and reacted with fatty acids in the cell membrane then forming malondialdehyde (MDA) at the initiation phase. In malignancy, the excessive expression of Bcl-2 can be found as one of at the initiation phase of carcinogenesis. Objective : To determine the differences in MDA levels, Bcl-2 tissue expression between control mice and mice that applied DMBA and topical cocoa extract with different concentrations. Method : The study sample was 30 Swiss albino mice, divided into 6 groups of 5 mice each: Group I without treatment, group II DMBA, III cacao 200 ppm and DMBA, IV cocoa 400 ppm and DMBA, V cocoa 800 ppm. Cocoa extract was applied everyday followed by DMBA with 1 day interval, all for 1 week. Result : In the experiment group, the lowest level of MDA is in the 200 ppm cocoa group (p ≤ 0.05). MDA level is increasing along with cocoa concentration, however at the highest cocoa concentration 800 ppm the average of MDA level is still lower than the DMBA group. Bcl-2 expression was shown in 60% of the subjects in the DMBA group, 40% of the subjects in the 200 ppm cocoa group, 20% in the 400 ppm and 800 ppm cocoa group. Conclusion : Topical application of cocoa extract has a protective effect in the initiation phase because there is a decrease in MDA levels at a concentration of 200 ppm. The expression of Bcl-2 decreased along with the increasing concentration of cocoa extract.

Chemopreventive action of non-steroidal anti-inflammatory drugs in 9,10-dimethylbenzanthracene induced lung carcinogenesis in BALB/C mice: Expression of COX-1, COX-2 and Nf-κB

Non-steroidal anti-inflammatory drugs (NSAIDs) play an effective chemopreventive action against a variety of cancers. The present study aimed at targeting pro-inflammatory cyclooxygenase (COX) and NF-kB mediated inflammatory pathways in 9,10-dimethylbenzanthracene (DMBA) induced lung cancer in BALB/C mice and chemoprotective action of NSAIDs. Animals were divided into five groups and treated with NSAIDs, intratracheally, daily for a period of 18 weeks. Group 1 as control, received vehicle treatment; Group 2 received single dose of DMBA (10mg/kg bw); Group 3, 4 and 5 besides DMBA treatment, also received Aspirin (60mg/kg bw), Celecoxib (6.0mg/kg bw) and Etoricoxib (0.6mg/kg bw), respectively. DMBA induce DNA damage, apoptosis and expression of COX-1, COX-2 and NF-κB using immunofluorescence and blot analysis were done. The present study demonstrated the formation of micronuclei, over-expression of COX-2 and NF-κB in DMBA induced lung tumorigenesis and thereby suggesting a marked role of inflammation in the tumour progression. Results indicate the formation of micronuclei in DMBA group, which were significantly reduced in aspirin treated group, and totally absent in the celecoxib and etoricoxib groups. In conclusion, co-administration of etoricoxib and celecoxib has significantly reduced the inflammatory potential of the growing neoplasm in DMBA induced lung cancer in male BALB/C mice.

Abyssinone V-4' Methyl Ether Isolated from Erythrina droogmansiana (Leguminosae) Inhibits Cell Growth and Mammary Glands Hyperplasia Induced in Swiss Mice by the 7,12-Dimethylbenz(a)anthracene.

There is a long standing interest in the identification of medicinal plants and derived natural products for developing cancer therapeutics. The present study was designed to evaluate the in vitro and in vivo antiproliferative effects of Abyssinone V-4' methyl ether (AVME) on breast tissue of mice. The cytotoxicity of AVME was evaluated using MTT assay in four cancer cell lines (DU145, PC3, HepG2, and MCF-7). Further, a protective effect of AVME was evaluated on 7,12-dimethylbenz(a)anthracene- (DMBA-) induced breast tumor in Swiss mice. Incidence, burden, volume, and histological analysis of mammary tumors were measured. As a result, AVME inhibits DU145, PC3, HepG2, and MCF-7 cells growth. In vivo, no tumor was detected in mice from the normal group as compared to those of DMBA group. Moreover, AVME inhibits the DMBA-induced mammary glands hyperplasia in mice at the dose of 10 mg/kg, evidenced by a decrease of tumor incidence, tumor weight, and volume as well as a protective effect against the lobular alveolar hyperplasia. Taken all together, these results suggest that Abyssinone V-4' methyl ether is endowed with antitumor properties and could be a source of traditional medicine which deserves to be more elucidated and explored in the foreseeable future.

Obesity enhances carcinogen 7, 12-Dimethylbenz [a] anthracene -induced tumorigenesis in vitro and in vivo

Growing body of evidence shows that extra adiposity influences on the progression of multiple cancers, including breast cancer. The aim of this study is to investigate whether obesity correlates with mammary tumor development in vitro and in vivo. We found that obesity-related mediators, 3T3-L1 adipocyte conditioned medium, enhanced formation of cancerous foci induced by the carcinogen 7,12-Dimethylbenz[a]anthracene (DMBA) in NIH/3T3 fibroblasts, in vitro. Additionally, we tested the effect of obesity in mouse model of DMBA-induced breast cancer. C57BL/6J female mice were fed a low fat (LF), or high fat (HF) diet, and DMBA was administered by oral gavage (LF plus DMBA [LFD] and HF plus DMBA [HFD]). Our results indicated that HFD mouse developed a tumor which weight was 169mg, whereas the LFD mouse developed a tumor weight of 77mg. Histological analysis of the mammary tumor from HFD group showed morphological aggressiveness and multiple cell type infiltration compared to LFD group. The epididymal adipose tissue from the DMBA groups showed more macrophage infiltration, polarized towards an M1 phenotype compared to the non-DMBA mice. HF mice showed less accumulation of M2 macrophages in the adipose tissue. In summary, obese mediators enhanced DMBA induced tumorigenesis in vitro and in vivo.

Dampness-Heat Accelerates DMBA-Induced Mammary Tumors in Rats.

To investigate the impact of dampness-heat (DH) on the development of mammary tumors in 7,12-dimethylbenz(a)anthracene (DMBA)-induced rats. Forty rats were randomly divided into 3 groups in a randomized block design, including the control group (n=13), DMBA group (n=14), and DMBA plus DH group (n=13). Rats in the DMBA group and DMBA plus DH group were intragastrically administrated with DMBA (100 mg/kg) for twice, once per week, while rats in the control group were treated with equivalent volumes of sesame oil. After DMBA administration, rats in the DMBA plus DH group were exposed to a simulated climate chamber with ambient temperature (33.0±0.5°C) and humidity (90%±5%) for 8 weeks, 8 h per day. The body weight, time of tumor formation, and number of tumors were measured weekly to calculate tumor incidence, average latency period, average number of tumors, and average tumor weight. At the end of the experiment, the levels of matrix metalloproteinase 9 (MMP-9) and tissue inhibitor of metalloproteinases 1 (TIMP-1) in serum, and the contents of tumor necrosis factor-α (TNF-α) and interleukin (IL)-1β in serum and tumor tissue were measured, respectively. Some tumor tissues were processed for hematoxylin-eosin staining to determine the histopathological changes. Compared with DMBA, DMBA plus DH significantly increased the average number of tumors, average tumor weight, levels of serum MMP-9, TIMP-1, TNF-α and IL-1β, and contents of tumor tissue TNF-α and IL-1β (P<0.05 or P<0.01). DH could accelerate the development of mammary tumors through increasing the expressions of MMP-9, TIMP-1, TNF-α and IL-1β in DMBA-induced rats.

EFEK KO-KEMOTERAPI FRAKSI ETIL ASETAT AKAR PASAK BUMI DAN DOXORUBICIN TERHADAP PROLIFERASI DAN EKPRESI BAX JARINGAN PAYUDARA TIKUS SD

The use of co-chemotherapy agent was needed since there were some toxicities on the normal tissues caused by the use of doxorubicin. The root of Eurycoma longifolia Jack, a part of plant, has a potential activity as co-chemotherapy. This study aimed to determine the effect of co-chemotherapy of ethyl acetate fraction of E. longifolia Jack roots and doxorubicin against cell proliferation activity by AgNOR method and determine expression of Bax protein of breast tissue in rats induced by DMBA. The rats were divided into five groups: I (baseline), II (DMBA 20 mg/kgBW), III (DMBA, doxorubicin 1.12 mg/kg), IV (DMBA, fraction of 100 mg/kg), and V (DMBA, doxorubicin, fractions). All the rats were sacrificed at week 16. Their breast tissue was evacuated. Cell proliferation and expression was observed using AgNOR method and immunohistochemistry, respectively. Results showed the percentage of p-AgNOR obtained by the healthy group, DMBA group, DMBA+Doxorubicin group, DMBA+ethyl acetate fraction of E. longifolia Jack root group, and DMBA+Doxorubicin+Ethyl acetate fraction of E. longifolia group were 0±0%, 14.67±2.11%, 1.83±1.21%, 6.83±2.03%, and 4.08±0.95%, respectively. The percentage of Bax expression obtained by the healthy group, DMBA group, DMBA+Doxorubicin group, DMBA+ethyl acetate fraction of E. longifolia Jack root group, and DMBA+Doxorubicin+Ethyl acetate fraction of E. longifolia group were 68.82±1.52%, 26.86±3.25%, 44.49±2.06%, 80.92±3.27%, and 78.70±4.87%, respectively. Based on the results, it was concluded that co-chemotherapy agent of ethyl acetate fraction of E. longifolia Jack roots and Doxorubicin could inhibit proliferation and trigger apoptosis through Bax expression in breast tissue of rats induced by DMBA.

Evaluation of the Black Cumin Seed Oil Role (BCSO) on a Decline in eNOS Expression and Plasma NO Levels: Initial Studies Kemopreventive BCSO for Lung Cancer

BCSO is effective as an anti-aging agent in cultures of endothelial and macrophage exposed 7.12, dimethyl-benzantracene (DMBA). Reactive radicals damage endothelial tissue, cause inflammatory reactions and have a role in carcinogenesis. Excessive eNOS expression linked to chronic inflammation and carcinogenesis of lung cancer. The research objective was to determine the effect of BCSO on the expression of eNOS and NO levels of macrophage SD rats exposed DMBA. A study used 36 rats SD that divided into 6 groups, given BCSO (0,01, 0,05 and 0.1 ml / day), positive, negative and normal control. Variables were serum levels of NO and eNOS expression in endothelial tissue. The results showed that eNOS expression in DMBA group is higher than the normal group (P <0.05). BCSO will decrease eNOS expression and NO levels. ENOS expression and NO levels in group BCSO 0,01 and 0,05 ml / kg body weight / day lower than the DMBA group (p 0.05). Conclusion: a dose BCSO can degrade endothelial eNOS expression and NO levels of macrophage culture supernatant SD rat DMBA induced

Modulating Effect of Hypnea musciformis (Red Seaweed) on Lipid Peroxidation, Antioxidants and Biotransforming Enzymes in 7,12-Dimethylbenz (a) Anthracene Induced Mammary Carcinogenesis in Experimental Animals.

Background:Breast cancer is the second most widespread diagnosed cancer and second leading cause of cancer death in women.Objective:The present work was carried out to evaluate the chemo preventive potential of Hypnea musciformis (ethanol extract) seaweed on oxidative stress markers, bio transforming enzymes, incidence of tumors, and pathological observation in 7,12-dimethylbenzanthracene (DMBA) exposed experimental mammary carcinogenesis.Materials and Methods:Female Sprague–Dawley rats were randomly divided into four groups. Rats in the group 1 served as control. Rats in the group 2 and 3 received a single subcutaneous injection of DMBA (25 mg/kg body weight (b.w)) in the mammary gland to develop mammary carcinoma. In addition, group 3 rats were orally administrated with 200 mg/kg between of H. musciformis along with DMBA injection and group 4 rats received ethanolic extract of H. musciformis every day orally (200 mg/kg b.w) throughout the experimental period of 16 weeks.Results:Our results revealed that treatment with H. musciformis ethanolic extract to DMBA treated rats significantly reduced the incidence of tumor and tumor volume as compared to DMBA alone treated rats. Moreover, our results showed imbalance in the activities/levels of lipid peroxidation by products, antioxidant enzymes, and bio transforming phase I and II enzymes in the circulation, liver and mammary tissues of DMBA treated rats which were significantly modulated to near normal on treatment with ethanolic extract of H. musciformis. All these alterations were supported by histochemical findings.Conclusion:The results obtained from this study suggest that chemo preventive potential of H. musciformis ethanol extract is probably due to their free radicals quenching effect and modulating potential of bio transforming enzymes during DMBA exposed experimental mammary carcinogenesis.SUMMARY DMBA is a source of well-established site specific carcinogenHypnea musciformis act as a free radical quencherHypnea musciformis has a definite chemo preventive efficacy in experimental ratsH. musciformis is a resource of prooxidant/antioxidant balance and also its anti-proliferative effectsH. musciformis has a detoxificant in the mammary carcinoma. Abbreviations Used: BRCA1: Breast Cancer Gene 1; BRCA2: Breast Cancer Gene 1; CYP: Cytochrome P450; DMBA: 7,12-Dimethylbenzanthracene; DMSO: Dimethyl sulfoxide; H2O2: Hydrogen peroxides; LPO: Lipid peroxidation; PAH: Polycyclic aromatic hydrocarbon; ROS: Reactive oxygen species; TBARS: Thiobarbituric acid reactive substances; GSSG: Oxidized glutathione.

Crystal structure and chemotherapeutic efficacy of the novel compound, gallium tetrachloride betaine, against breast cancer using nanotechnology.

The objective of this study was to investigate the antitumor efficacy of a novel synthesized compound, betaine gallium-tetrachloride (BTG), alone or combined with ZnO-nanoparticles (BTG + ZnO-NPs) on the incidence of 7, 12-dimethylbenz-anthrathene-induced mammary tumor in female rats. Crystal and molecular structure of the prepared BTG were identified using X-ray crystallography. In vitro study revealed BTG more cytotoxic than BTG + ZnO-NPs on human breast cancer (MCF-7) cell line. In vivo study demonstrated that the blood antioxidant status of tumor-bearing rats (DMBA group) was significantly lower than normal noticeable by a significant decrease in GSH content, GPx, SOD, and CAT activities associated with a significantly high MDA content. Both treatments have significantly elevated SOD and CAT activities with a concomitant decrease of MDA level compared to DMBA group. However, BTG + ZnO-NPs accentuated the decrease of GSH regarding DMBA group. The results showed also that both treatments significantly activate caspase-3 enzyme and apoptosis in mammary glands. Their administration to tumor-bearing rats was found to significantly reduce plasma iron and iron-binding capacity (TIBC) compared to DMBA group. Regarding liver function, both treatments significantly reduced the increase of ALT and AST activities compared to DMBA group. However, BTG + ZnO-NPs decreased albumin below normal level. Histopathological studies showed that normalization of tissue structures was higher in BTG than BTG + ZnO-NPs treatment. According to the results obtained, it is observed that the antitumor effect of BTG alone was as strong as BTG + ZnO-NPs and even more efficient in some aspects accordingly, a combination is not needed. Thus, the novel synthetic gallium derivatives may potentially present a new hope for the development of breast cancer therapeutics, which should attract further scientific and pharmaceutical interest.

Ameliorative potential of fluoxetine/raloxifene combination on experimentally induced breast cancer.

Breast cancer is one of the most common types of malignancies in females worldwide. Targeting the estrogen receptors alone with raloxifene (RAL) reduces the incidence of estrogen receptor positive tumors. Fluoxetine (FLX) is one of selective serotonin reuptake inhibitors that was proven to have anticancer properties. Our aim was to detect the effects of RAL/FLX combination on experimentally induced breast cancer. Eighty female Wistar rats were divided into four equal groups: 7,12-Dimethyl Benzanthracene (DMBA) induced breast cancer group, DMBA+RAL, DMBA+FLX and DMBA+RAL+FLX. Tumor volume, tissue malondialdehyde (MDA), catalase (CAT), superoxide dismutase (SOD), tumor necrosis factor-alpha (TNF-α), interleukin 6 (IL-6) and transforming growth factor beta1 (TGF-β1) were determined in the tumor tissues. Parts of the tumor were subjected to histopathological examination. RAL or FLX alone or in combination induced significant increase in tumor CAT and SOD with significant decrease in tumor volume, tissue MDA, TNF-α, IL-6 and TGF-β1 and alleviated the histopathological and immunohistochemical changes compared to DMBA group. In conclusion, RAL/FLX combination had a better effect than each of RAL or FLX alone against DMBA-induced breast cancer in rats which may represent a new therapeutic modality for management of breast cancer.

Celecoxib and fish oil: a combination strategy for decreased inflammatory mediators in early stages of experimental mammary cancer

Chronic inflammation has been directly linked to cancer progression. Therefore, current study was designed to understand the mechanism of action of chemo-preventive effect of celecoxib and fish oil on inflammatory mediators in experimental mammary carcinoma. Female Wistar rats were distributed into control and DMBA treated groups and further subdivided based on pretreatment with celecoxib and/or fish oil. Inflammation was measuredby assessing expression of NF-κB, COX-2 and cytokines. The results indicated an elevation in expression of NF-κB, COX-2 and cytokines' levels (IFN-γ, IL-4 and IL-10) in DMBA group as compared to controls. On pretreatment with celecoxib and/or fish oil in DMBA treated animals, a significant reduction in expression of NF-κB, COX-2 and cytokines' levels was observed. The decrease was more pronounced with combinatorial regimen than either celecoxib or fish oil alone. To conclude, a combinatorial strategy of celecoxib and fish oil may generate an immune response against the tumor cell by altering cytokine repertoire and decrease the tendency of tumor cells to escape immune surveillance.

ANTIBREAST CANCER ACTIVITY OF NANOPROPOLIS INDONESIA ON INDUCED MAMMARY GLAND TUMOR BY DMBA IN VIRGIN SPRAGUE-DAWLEY RATS

The objective of this study was to determine the effect of nanopropolis to cure cancer induced on rat mammary tumor using 7,12-dimethylbenz(a)anthracene (DMBA). After the first tumors appearance, twenty eight rats were divided into seven groups. Group 1, 2 and 3 served as recipient of nanopropolis dosages 8, 32 and 56 µg/mL treatments; Group 4 served asrecipient of propolis dosage of 233 µg/mL treatment; Group 5 served asrecipient of doxorubicin treatment; Group 6 served as recipient of DMBA treatment and Group 7 as normal group (control). The effect of nanopropolis dosage of 32 µg/mL and propolis dosage of 233 µg/mL were similar in reducing tumor size, healing the wounds caused by the tumor and eliminating cancer cells. It turns out that there is a relationship between particle size absorbent materials. The study suggested that nanopropolis with small concentration was very effective to treatrat mammary gland tumors and breast cancers.Keywords: breast cancer, nanopropolis, propolis, Sprague-Dawley rat

Modulatory effect of Pleurotus ostreatus on oxidant/antioxidant status in 7, 12-dimethylbenz (a) anthracene induced mammary carcinoma in experimental rats--A dose-response study.

Worldwide, breast cancer is the second most prevalent cancer among women and its incidence is increasing alarmingly. 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. 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. 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). 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. 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.

Abstract 5345: DMBA promotes erbB-2 mediated carcinogenesis through activation of estrogen receptor and receptor tyrosine kinase pathways

Abstract ErbB-2 is a receptor tyrosine kinase (RTK) that is amplified/overexpressed in 20-30% of all invasive breast malignancies; it has been associated with poor prognosis and therapeutic resistance in breast cancer patients. 7,12-dimethylbenz anthracene (DMBA) is a polycyclic aromatic hydrocarbon known for its carcinogenic effects. The objective of this study was to investigate the effect of DMBA exposure on erbB-2 mediated carcinogenesis. This represents a combination of genetic predisposition and environmental assault that synergistically promote carcinogenesis. In this study, female MMTV-erbB-2 transgenic mice at 6-weeks of age were treated weekly by oral gavage with either 1.0 mg DMBA in peanut oil or vehicle alone for 6 weeks. In the control group, palpable tumors appeared at week 25, with an average latency of 36.0 weeks. All mice in the DMBA group developed mammary tumors between week 16 and 26 with an average latency of 20 weeks. By the endpoint (first tumor ∼1.5cm3), the average number of palpable tumors per mouse were 1.15 and 2 for control and DMBA groups, respectively. Lung metastasis in the DMBA group was significantly higher than control mice (40% DMBA vs. 5% control). These data show that DMBA exposure significantly promoted erbB-2 mediated carcinogenesis. Whole mount analysis showed that at 14 weeks of age there was marked expansion of the ducts, whereas lateral branching of mammary glands from DMBA mice appeared to be inhibited, suggesting that DMBA stimulates glandular growth while inhibiting differentiation in this model. Western blot analysis of mammary tissues at 14 weeks of age showed that ERα, p-ERα, cyclin D1, Bcl-2, c-myc, EGFR, erbB-2 and erbB-3 protein levels were significantly increased in DMBA treated mice, which was accompanied by increased phosphorylation/activation of erbB-2, EGFR, ERK and Akt1. These data suggest that DMBA induced activation of both ER and receptor tyrosine kinase (RTK) pathways. Interestingly, tumor histology between tumors from control and DMBA treated mice was similar. However, analysis of tumor karotypes from control and DMBA mice showed that tumors from DMBA mice displayed more chromosomal alterations; an addition to chromosome 4 and trisomy 5 in the control mouse, trisomy 2, trisomy 3 and a deletion to chromosome 4 were detected from tumors of the DMBA mice, suggesting that DMBA induced chromosomal instability contributed to tumor promotion in this model. Taken together, our data suggest that DMBA promoted erbB-2 mediated carcinogenesis. In addition to its well known mutational effect, DMBA induced deregulation of ER and erbB-2 pathways plays a critical role in this process. Citation Format: Zhikun Ma, Stanley Kosanke, Morgan Carrington, Xiaohe Yang. DMBA promotes erbB-2 mediated carcinogenesis through activation of estrogen receptor and receptor tyrosine kinase pathways. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 5345. doi:10.1158/1538-7445.AM2014-5345

Thymoquinone, a component of the Middle East spicy seed Nigella sativa, decreases oxidative DNA damage in a rat model of mammary cancer (693.21)

Tamoxifen (TAM) is used widely for treatment and prevention of breast cancer. However, TAM has been reported to have a negative effect on the antioxidant glutathione (GSH) levels and 8‐hydroxydeoxyguanosine (8‐OHdG), a fingerprint of free radial attack on DNA. Thymoquinone (TQ), the main active ingredient of Nigella sativa, is used in the Middle East for treatment of several diseases like cancer. The aim of my research was to investigate the role of TQ in improving 8‐OHdG and GSH compared with TAM in female Sprague Dawley rats treated with DMBA, a drug used to induce mammary carcinoma in experimental rodents. Five groups of 10 rats (Controls, DMBA, TAM, TQ, and TAM+TQ) were treated for 10 weeks after injection of DMBA. 8‐OHdG in blood samples was significantly higher in the TAM group compared with the controls (P=0.008), the DMBA group (P=0.041), and the TQ group (P &lt;0.001). TQ significantly decreased 8‐OHdG by itself compared with DMBA (P=0.039) and TAM (P=0.001), but did not significantly reduce the effect of TAM in the TAM+TQ group. On the other hand, GSH did not differ among treatments. Body weight gain over 12 weeks was significantly different among the groups (P&lt;0.001). The TAM and TAM+TQ groups had the lowest weight gain compared with the other groups. This is the first study to show that TQ protects against oxidative DNA damage. I conclude that TQ could be a better anticancer drug than TAM because it decreased 8‐OHdG and protected growth.

Breast cancer prevention with Morinda citrifolia (noni) at the initiation stage

Background: It has been reported that noni has multiple health benefits for over 2000 years. In this study, the cancer preventive effects of Tahitian noni® juice (TNJ) at the initiation stage on DMBA-induced mammary tumorigenesis in female SD rats was investigated.Objective: We took advantage of the DMBA-induced mammary carcinogenic model to study the preventive effects of TNJ at the initiation stage of mammary carcinogenesis in female SD rats by using clinical observation, pathological examination, and 32P-postlabeling assay.Methods: One hundred and sixty female SD rats were divided into eight groups with 20 rats in each group. Three doses of TNJ or placebo was given to the animals at the age of 35 days until the end of the experiment. When the animals were 55 days old, 25 mg/kg DMBA was fed to the animals in the DMBA group, placebo, and TNJ groups. The 20 rats were kept at age-matched controls. Palpable tumors were examined twice a week after DMBA administration in each group by an experienced professional. The size of tumor was measured by a graduated caliper. A piece of tumor, vascularization area, and mammary glands in the thoracic and abdomen areas of each rat were dissected respectively and fixed in 10% neutral buffered formalin for light microscope examination. The DMBA-DNA adduct formation in mammary tissues was detected by 32P-postlabeling assay.Results: The tumor latency in TNJ groups was delayed about 60-90 days when compared with positive controls. The number of palpable tumors per group was significantly reduced by 73%, 72% and 80% in 3%, 5%, and 10% TNJ groups respectively when compared with positive controls at the end of 330 days after DMBA administration. The number of palpable tumors in the placebo groups was slightly reduced in the early stage, but much less than that in the TNJ groups. The multiplicity and malignancy of lesions were significantly reduced and the survival rate of animals in the TNJ groups was significantly increased compared with positive controls at different time points. Histological examination showed that the malignancy of lesions in TNJ groups did not show a significant change when compared with that in positive and placebo groups. Conclusion: In conclusion, this is the first study which indicates that TNJ possesses a cancer preventive effect at the initiation stage of chemical carcinogenesis induced by DMBA in female SD rates. Key words: Morinda citrifolia, Tahitian noni® juice, breast cancer, cancer prevention

Antiproliferative Activity of Black Seed (Nigella sativa) on 7,12-dimethylbenz-[a]antracene (DMBA) Induced Mice Lung Cell

Lung cancer is the leading cause of death in the world. Nigella sativa is a plant that has an anticancer activity. Previous research showed that the chloroform extract of N. sativahave cytotoxic effect on T47D cells. This study aimed to observe the effect of cloroform extract of N. sativaseed (NSS) on mice lung cell after initiation of 7,12-dimethylbenz [a] anthracene. Sprague Dawleystrain female rats were divided intofive groups. Each group consisted of 12 rats. The experiment consisted of five mice groups, corn oil as a solvent control group, the DMBA dose 20 mg/kgBW p.o. twice a week during five weeks, DMBA+NSS dose 250 mg/kgBW, DMBA+NSS dose 500 mg/kgBW, and DMBA+NSS dose 750 mg/kgBW. Extract which was dissolved into corn oil was administered daily by the oral route 1 week before and during the DMBA induction. At the end of the study, the experimental mice were sacrified and colon organs were collected and then stained with Haematoxylin and Eosin (H&E) and AgNOR method. H&E staining showed there was a decrease damage inthe treatment group compare with DMBA group. In AgNOR staining result showed mAgNOR value in DMBA group was 1.47±0.558, in extract group (250, 500 and 750mg/kgBB) was 0.44±0.172, 1.38±0.140 and 1.25±0.164 respectively and in corn oil group was 0.65±0.050. The results showed that N. sativareduced the damage of colon cells and inhibit colon cell proliferation on mice induced DMBA. This study indicated that N. sativacan be developed into a chemopreventive agent for lung cancer.

Effects of propolis on lingual mucosa response of hamsters submitted to experimental carcinogenesis

To assess the tissue reaction of the lingual mucosa in hamsters submitted to daily, alternating, topical applications of 9,10-dimethyl-1,2-benzanthracene (DMBA) and a commercial brand of an ethanol propolis extract (EPE). A total of 60 hamsters were divided into three groups with two experimental periods (13 and 20 weeks). The lateral edge of the tongue was submitted to daily, alternating, topical applications of 0.5% DMBA and 30% EPE (EPE group, n=20), 0.5% of DMBA and aqueous propolis extract (APE group, n=20) and 0.5% of DMBA and saline solution (DMBA group, n=20). The occurrence of clinical and histological alterations was analyzed, along with the measurement of the area and volume of the clinical alterations, the determination of structural and cytological alterations of the squamous epithelial tissue with atypias and the measurement of the histological area of squamous cell carcinomas. There were no significant differences among groups regarding any of the variables analyzed in the two evaluation periods. At week 13, a single squamous cell carcinoma occurred in the EPE group. At week 20, the greatest occurrence of squamous cell carcinoma was also in the EPE group. The mechanism of EPE (30% alcohol content) affecting the onset of tissue reaction and the promotion of carcinogenesis has not been clarified yet.

Chemopreventive efficacy of Phyllanthus emblica L. (amla) fruit extract on 7,12-dimethylbenz(a)anthracene induced oral carcinogenesis – A dose–response study

Phyllanthus emblica L. (Euphorbiaceae), a novel natural fruit has long been used as a home remedy by the medical practitioners. In this report, we investigated the chemopreventive effect of P. emblica fruit methanolic extract (PFMet) on oxidant–antioxidant status in hamster buccal pouch carcinogenesis. Buccal pouch carcinoma was induced in hamsters by painting with DMBA (0.5% in mineral oil) on the left buccal pouch three times a week for 14 weeks. By means of HPLC analysis, ascorbic acid (24.13%), gallic acid (10.45%), ellagic acid (1.74%) and quercetin (0.009%) were identified and quantified in the PFMet. The results showed that depleted activities of SOD, CAT and TBARS level and significant elevation were observed in the levels of GSH, vitamin E and activity of GPx in DMBA group of buccal pouch. The level of TBARS was significantly enhanced and the activities of enzymatic (SOD, CAT and GPx) and non-enzymatic (vitamin E, vitamin C and GSH) antioxidants were diminished significantly in plasma of tumor bearing animals. The effects were dose dependent and the above noted parameters were renovated to near normal after supplementation with different doses of PFMet (50, 100 and 200mg/kg BW). The data obtained in this study clearly indicate that PFMet at a dose of 200mg/kg BW possesses optimum chemopreventive effect against DMBA-induced buccal pouch carcinogenesis.

Lycopene counteracts the hepatic response to 7,12-dimethylbenz[a]anthracene by altering the expression of Bax, Bcl-2, caspases, and oxidative stress biomarkers

Context: Lycopene is a carotenoid found in tomato, watermelon, pink grapefruit, and guava in high concentration. Dietary intake of lycopene has been proposed to inversely correlate with the risk of cancer. It has also been reported to provide protection against cellular damage caused by reactive oxygen species, which makes it worthwhile to study the effect of lycopene on liver damage in rat model.Objective: In this study, we report the effect of lycopene on 7,12-dimethylbenz[a]-anthracene (DMBA)-induced expression of Bax, Bcl-2, caspases, and oxidative stres biomarkers in the liver.Materials and methods: Lycopene was administered orally at 20 mg/kg body weight for 20 weeks followed by the intraperitoneal injection of DMBA (50 mg/kg body weight) on day 1 and day 30 of the experiment. Control rats received vehicle (olive oil) or DMBA alone. Rats were sacrificed after completion of the treatment.Results: We observed that the levels of Bax, caspase-3, and caspase-9 decreased to 44, 67, and 43%, respectively, and Bcl-2 increased by 80% in DMBA-treated rats. Lycopene reversed the changes in the respective groups, and decreased the level of Bcl-2 to 25%, while increasing the Bax to 42% when compared to DMBA control. Lycopene increased the expression of caspase-3 (82.09%) and caspase-9 (58.96%), and attenuated the level of hepatic malondialdehyde (41%) and 8-isoprostane (40%) when compared to the respective controls. Glutathione (GSH) decreased significantly in DMBA group (15.89%), but reached the normal level in lycopene-treated animals. Hepatic lycopene concentration in treated rats was 8.2 nmol/g tissue.Conclusion: The study reports that lycopene counteracts the hepatic response to DMBA by altering the expression of Bax, Bcl-2, caspases, and oxidative stress biomarkers in animal model.