• Korean Journal of Veterinary Research
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• v.41 no.4
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• pp.549-555
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• 2001

Indole-3-carbinol (I3C), one component of cruciferous vegetables (the Fammily of Cruciferae), has been shown to exert its chemopreventive effect in liver, colon and mammary tissue before or concurrent exposure of carcinogen, but there have been several evidences that consumption of I3C induced tumor promotion in some tissues. Our studies were investigated to examine the modifying effects of I3C in the 7,12-dimethylbenz[$\alpha$]anthracene (DMBA) induced rat mammary gland tumor model. Fifty-two female Sprague-Dawley rats were randomly divided into five groups. Animals of the group 1 were given the diet containing 100ppm I3C and animals of the groups 2 and 4 were given the diet containing 300ppm I3C from 6 weeks of age. At 7 weeks of age, the animals of the groups 1, 2 and 3 were intubated with DMBA. All amimals were killed at 20 weeks after carcinogen treatment. There were significant increases of food consumption in I3C feeding groups compared with those of basal diet feeding groups. The incidences of the mammary tumors in the group 1, 2 and 3 were 75.0% (9/12), 56.3% (9/16) and 93.8% (15/16), respectively and the average number of tumors of group 1 (DMBA+I3C 100ppm: $2.08{\pm}0.61$) and 2 (DMBA+I3C 300ppm: $1.19{\pm}0.32$) were significantly lower than that of group 3 (DMBA alone: $4.63{\pm}0.72$) at the value of P<0.05 and P<0.001, respectively. In the pathological examination of appearing tumors, most of them were adenocarcinoma. Many epithelial cells of tumors showed strong estrogen receptor (ER) $\alpha$ expression but there were slight difference of ER $\alpha$ expression among the type of tumors. We suggest that pre-initiation treatment of I3C has an inhibitory effects on mammary carcinogenesis induced by DMBA.

• Toxicological Research
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• v.16 no.4
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• pp.275-284
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• 2000

The organ culture model of the whole mammary gland has many advantages for the study of branching morphogenesis and biological characteristics, including tumorigenesis. Prior to whole gland organ culture, rats were treated with 7,12-dimethylbenz[a]anthracene (DMBA) or N-methyl-N-nitrosourea (MNU) for one week. The tramdorming effect and the morphological changes were assessed by the whole mount preparations and histopathological examination in terminal end buds (TEB), terminal ducts (TD), alveolar buds (AB), alveolar lobules (AL) and hyperplastic alveolar nodules (HAN) of the mammary gland. Grossfindings of the mammary glands at dissection were higher branching morphogenesis and larger volume in carcinogen-treated groups than in carcinogen-non-treated groups. Results of the whole mount method were coincided with those of the histopathological observations. Circular TEB, normally maintained AB, AL, and high cellular density were more frequently observed in carcinogen-treated groups than in carcinogen-nan-treated groups. Histopathologically, as a preneoplastic marker, HAN was maintained only in mammary organ culture of the carcinogen-treated groups. These findings suggest that in vivo trans-formation effects by carcinogens persisted during the mammary organ culture. These results were more characteristic in DMBA than in MNU-treated group. Ducts and terminal ducts appeared to have lost morphology during their growths in case of without diethylstilbestrol (DES). The fact that in vitro organ culture without DES was resulted in abnormal ductular morphogenesis confirms that DES is a physiological regulator of ductular epithelial cell growth.

• Nutritional Sciences
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• v.9 no.1
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• pp.14-19
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• 2006

Breast cancer may be the consequence of free radical damage, which is partially caused by the excessive intake of dietary fat and imbalances in antioxidant scavenger system;. In this experiment, we examined! the effects of dietary peroxidizability index (PI) values on hepatic thiobmbituric acid reaction substances (TBARS) and antioxidant enzyme activities in rats treated with 7,12-dimethylbenz[$\alpha$]anthracene (DMBA). Female Sprague-Dawley rats were used and 7,12-DMBA (20 mg/kg body weight) was gastrically intubated at seven weeks of age in order to induce mammary tumors (MT). The levels of dietary PI were 36, 81, 126 and 217 (LPI, MLPI, MHPI and HPI), while dietary polyunsaturated/saturated fatty acids ratio was maintained at the same level (1.0). Fat used in the experiment was mixed with soybean oil, com oil, palm oil, perilla oil, sesame oil, fish oil, and beef tallow. Experimental diets were given for the following 20 weeks. We measured tumor numbers and weights, and then assayed the hepatic TBARS levels and antioxidant enzyme activities such as superoxide dismutase (SOD), catalase, glutathione peroxidase, glutathione-S-transferase (GST) and glutathione reductase (GR). The incidence of Mr was the lowest in the MHPI group. The hepatic TBARS level was significantly raised with increasing dietary PI value. The hepatic SOD and GR activities were differed significantly by dietary PI value. The hepatic SOD activity was negatively correlated with dietary PI value and GR activity was the highest in the rats fed the MHPI diet. When the dietary P/S ratio is kept at 1.0, adequate dietary PI value (PI value of 126) may reduce the incidence and growth of Mr, but this benefit may be lost with higher dietary PI value. These results suggest that the awareness of dietary PI values may help to decrease breast cancer incidence and growth.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.6
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• pp.2533-2539
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• 2012

Annona muricata L (Annonaceae), commonly known as soursop has a long, rich history in herbal medicine with a lengthy recorded indigenous use. It had also been found to be a promising new anti-tumor agent in numerous in vitro studies. The present investigation concerns chemopreventive effects in a two-stage model of skin papillomagenesis. Chemopreventive effects of an ethanolic extract of A. muricata leaves (AMLE) was evaluated in 6-7 week old ICR mice given a single topical application of 7,12-dimethylbenza(${\alpha}$)anthracene (DMBA 100ug/100ul acetone) and promotion by repeated application of croton oil (1% in acetone/twice a week) for 10 weeks. Morphological tumor incidence, burden and volume were measured, with histological evaluation of skin tissue. Topical application of AMLE at 30, 100 and 300mg/kg significantly reduced DMBA/croton oil induced mice skin papillomagenesis in (i) peri-initiation protocol (AMLE from 7 days prior to 7 days after DMBA), (ii) promotion protocol (AMLE 30 minutes after croton oil), or (iii) both peri-initiation and promotion protocol (AMLE 7 days prior to 7 day after DMBA and AMLE 30 minutes after croton oil throughout the experimental period), in a dose dependent manner (p<0.05) as compared to carcinogen-treated control. Furthermore, the average latent period was significantly increased in theAMLE-treated group. Interestingly, At 100 and 300 mg/kg, AMLE completely inhibited the tumor development in all stages. Histopathological study revealed that tumor growth from the AMLE-treated groups showed only slight hyperplasia and absence of keratin pearls and rete ridges. The results, thus suggest that the A.muricata leaves extract was able to suppress tumor initiation as well as tumor promotion even at lower dosage.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.1
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• pp.117-123
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• 2016

Taxol (paclitaxel) is a powerful anti-cancer drug widely used against several types of malignant tumors. Because Taxol may exert several side effects, a variety of formulations have been developed. One of these features liposomes, regarded as one of the most promising drug carriers, biocompatible and best able to reduce drug toxicity without changing efficacy against tumor cells. Eruca sativa seed extract (SE) is considered a promising natural product from cruciferous vegetables against breast cancer, increasing chemotherapeutic and eliminating harmful side effects. The effects of Taxol-encapsulated liposomes (T) alone and in combination between Eruca sativa seed extract on nuclear factor kappa B (NF-${\kappa}B$), cyclooxygenase-2 (COX-2) and B-cell lymphoma-2 (Bcl-2) gene expression levels were investigated in rat mammary gland carcinogenesis induced by 7,12 dimethylbenz(${\alpha}$) anthracene (DMBA) using qRT-PCR. The results showed that DMBA increased NF-${\kappa}B$, COX-2 and Bcl-2 gene expression levels and lipid peroxidation (LP), while decreasing glutathione-S-transferase (GST) and superoxide dismutase (SOD) activities and total antioxidant concentration (TAC) compared to the control group. T and T-SE treatment reduced NF-${\kappa}B$, COX-2 and Bcl-2 gene expression levels and LP. Hence, T and T-SE treatment appeared to reduce inflammation and cell proliferation, while increasing apoptosis, GST and SOD activities and TAC.

• The Korean Journal of Pharmacology
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• v.28 no.2
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• pp.213-222
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• 1992

We investigated effects of several chemical carcinogens, i.e., $benzo({\alpha})pyrene$ (BP),7,12-dimethylbenz(a)anthracene (DMBA), nitrosomethyl urea (NMU), and nicotine on the replication, cytolyticity, DNA synthesis, and protein synthesis of type 1 herpes simplex virus (HSV-1) in viral infected Vero cell monolayers. We observed that the BP and DMBA did not show such activity. All chemical carcinogens did not inhibit the synthesis of viral DNA, but the expression of gamma viral proteins that are expressed from the newly synthesized progeny viral DNA was somewhat notably inhibited by BP and DMBA. However, the synthesis of alpha and beta viral proteins was not altered by the chemical carcinogens. These data indicate that the gamma viral proteins expressed from the newly synthesized DNA in the presence of chemical carcinogens in the culture medium may be defective. This is further supported by the fact that the virus fail to replicate in the presence of these chemical carcinogens, in spite of viral DNA and proteins are somewhat normally synthesized.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.4
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• pp.2249-2254
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• 2013

The study was conducted to determine the effect of Malaysian jungle Tualang Honey (TH) on development of breast cancer induced by the carcinogen 7,12-dimethylbenz(${\alpha}$)anthracene (DMBA) in rats. Forty nulliparous female Sprague-Dawley rats were given 80 mg/kg DMBA then randomly divided into four groups: Group 1 served as a Control while Groups 2, 3 and 4 received 0.2, 1.0 or 2.0 g/kg bodyweight/day of TH, respectively, for 150 days. Results showed that breast cancers in the TH-treated groups had slower size increment and smaller mean tumor size (${\leq}2cm^3$) compared to Controls (${\leq}8cm^3$). The number of cancers developing in TH-treated groups was also significantly fewer (P<0.05). Histological grading showed majority of TH-treated group cancers to be of grade 1 and 2 compared to grade 3 in controls. There was an increasing trend of apoptotic index (AI) seen in TH-treated groups with increasing dosage of Tualang Honey, however, the mean AI values of all TH-treated groups were not significantly different from the Control value (p>0.05). In conclusion, Tualang Honey exerted positive modulation effects on DMBA-induced breast cancers in rats in this preliminary study.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.5
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• pp.3123-3129
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• 2013

Background: The search for naturally occurring agents in routinely consumed foods that may inhibit cancer development is of high priority. [6]-Paradol is a pungent phenolic bioactive component from ginger with welldocumented health promoting antioxidant, antimutagenic, antigenotoxic and anti-inflammatory properties. However, anticarcinogenic effects have yet to be fully explored. The objectives of the present study were therefore to assess protective effects against 7,12-dimethylbenz(a)anthracene (DMBA) induced buccal pouch carcinogenesis in male golden Syrian hamsters. Methods: Oral squamous cell carcinomas developed in the left buccal pouch of hamsters on painting with 0.5% of DMBA, three times in a week. To assess the apoptotic associated gene expressing potential of [6]-paradol, it was orally administered to DMBA treated hamsters on alternate days from DMBA painting for 14 weeks. Results: We observed 100% tumor formation with marked levels of neoplastic changes and altered the expression of apoptotic associated gene (p53, bcl-2, caspase-3 and TNF-${\alpha}$) was observed in the DMBA alone painted hamsters as compared to control hamsters. Oral administration of [6]-paradol at a dose of 30 mg/kg b.wt to DMBA treated animals on alternative days for 14 weeks significantly reduced the neoplastic changes and improved the status of apoptosis associated gene expression. Conclusion: These observations confirmed that [6]-paradol acts as a tumor suppressing agent against DMBA induced oral carcinogenesis. We also conclude that [6]-paradol also effectively enhances apoptosis- associated gene expression in DMBA treated animals.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.18
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• pp.8411-8418
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• 2016

The effect of Eruca sativa seed extract (SE) on nuclear factor kappa B (NF-${\kappa}B$), cyclooxygenase-2 (COX-2) and B-cell lymphoma-2 (Bcl-2) gene expression levels was investigated in rat mammary gland carcinogenesis induced by 7,12 dimethylbenz(${\alpha}$)anthracene (DMBA). DMBA increased NF-${\kappa}B$, COX-2 and Bcl-2 gene expression levels and lipid peroxidation (LP), while, decreased glutathione-S-transferase (GST) and superoxide dismutase (SOD) activities and total antioxidant concentration (TAC) compared to the control group. After DMBA administration, SE treatment reduced NF-${\kappa}B$, COX-2 and Bcl-2 gene expression levels and LP. Hence, SE treatment reduced inflammation and cell proliferation, while increasing apoptosis, GST and SOD activities and TAC. Analysis revealed that SE has high concentrations of total flavonoids, triterpenoids, alkaloids and polyphenolic compounds such as gallic, chlorogenic, caffeic, 3,4-dicaffeoyl quinic, 3,5-dicaffeoyl quinic, tannic, cinnamic acids, catechin and phloridzin. These findings indicate that SE may be considered a promising natural product from cruciferous vegetables against breast cancer, especially given its high antioxidant properties.

• Nutritional Sciences
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• v.5 no.2
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• pp.53-59
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• 2002

This study was conducted to examine the effects of dietary sources of fatty acids and protein on serum protein profiles, hepatic functional enzyme activities, mammary tumor incidence and tumor weight in 7, 12-dimethylbenz($\alpha$)anthracene (DMBA)-treated rats. The sources of dietary fatty acids were 18n6 (rich in linoleic acid), 18n3 (rich in linolenic acid) and 22n3 (rich in DHA) : sources of dietary protein were casein (C) and soy protein isolate (S). mammary tumors (MTs) were chemically induced by DMBA (9 mg/100 g body weight) which was gastrically intubated at 7 weeks of age. Each experimental diet was given for the following 25 weeks. Casein-fed rats (group C) exhibited significantly higher levels of weight gain and FER (food efficiency ratio) than did group S. Group C showed higher levels of serum protein and globulin, and higher albumin/globulin (A/G) ratios than group S. Liver functional enzyme activities (GOT, GPT, ALP, LDH, $\gamma$-GT) and LDH/GOT ratios were not influenced by dietary protein. GPT activity was lower in the group given 18n3, and ALP activity was lower in the group given 18n6. The incidence and total number of MTs appeared to be lower in the group given 22n3 than in the group given 18n3 or 18n6, even though the average weight of MTs was highest in the group given 22n3, The average weight of MTs was higher in the C group than in the S group. MT incidence had a positive correlation with LDH activity and LDH/GOT ratio. The average weight of MTs had a negative correlation with serum albumin levels and A/G ratios, and a positive correlation with ALP activity. This research suggests that the measurement of serum protein profiles and liver functional enzyme activities may be utilized to monitor the development of mammary tumors.