Showing papers on "7,12-Dimethylbenz[a]anthracene published in 2018"

Chemopreventive and anti-breast cancer activity of compounds isolated from leaves of Abrus precatorius L.

Abstract: The present study focuses on isolation and evaluation of the anti-cancer activity of compounds from the leaves of Abrus precatorius. The bioassay-directed strategy was adopted using chromatographic, gas chromatographic–mass spectrum analysis, nuclear magnetic resonance and X-ray crystallography techniques for purification and characterization of active cytotoxic compounds. Further, MDA-MB-231 breast cancer cell lines and 7,12-dimethylbenz (a) anthracene (DMBA) induced virgin female Sprague Dawley (SD) rats were used for in vitro and in vivo cytotoxicity evaluation. Stigmasterol hemihydrate and 9,12-Octadecadienoic acid (Z,Z)-2-hydroxy-1-(hydroxymethyl)ethyl ester or (β-monolinolein) were the two main cytotoxic constituents of leaf extract of A. precatorius, with an IC50 value of 74.2 and 13.2 µg/ml, respectively, in MDA-MB-231 cells. Additionally, the treatment with the stigmasterol and β-monolinolein as a combinatorial drug therapy in DMBA-induced female SD rats led to recovery of body weight, decreased tumor weight and volume, without any toxic side effects. Immunohistochemical examination showed extensive cell death and low proliferation in the treated tumor tissues that was confirmed by results from H and E staining, TUNEL assay and Ki-67 index as compared to control animal group. The reversion of glycoprotein, lysosomal and tumor marker enzyme levels back to near-normal levels after treatment with the plant compounds clearly demonstrated the reduction of tumor burden in these animals. This is the first report on isolation and characterization of the two active cytotoxic components from leaves of A. precatorius. Additionally, the profound cytotoxic and tumor-suppressive effect of these two compounds as a combinatorial therapy provide an alternative option for breast cancer treatment.

Syringic acid may attenuate the oral mucosal carcinogenesis via improving cell surface glycoconjugation and modifying cytokeratin expression.

Abstract: Syringic acid (SRA) is an excellent anti-oxidant and anti-cancer property in various in vitro and in vivo studies. In the present study was modifying effect of SRA on 7,12-dimethylbenz(a)anthracene (DMBA) induced cell surface glycoconjugates (GCs) abnormalities in the plasma and buccal mucosa of golden Syrian hamster buccal pouch carcinogenesis (HBPCs). Topical application of DMBA three times a week for 10 weeks on the buccal pouches of the hamsters resulted in well developed squamous cell carcinoma. GCs status was assessed biochemically, histological and immunoexpression pattern of cytokeratin (CK) in the buccal mucosa of the DMBA treated hamsters. Elevated levels of GCs and CK expression were observed in DMBA alone treated hamsters. Oral pre-administration of SRA (50 mg/kg bw) positively modulates the GCs levels and CK expressions to near normal. The present findings suggested that SRA can protect cell surface GCs and CK expression during DMBA induced HBPCs.

Effect of allyl isothiocyanate on NF-κB signaling in 7,12-dimethylbenz(a)anthracene and N-methyl-N-nitrosourea-induced mammary carcinogenesis.

Abstract: Background Inflammation plays a pivotal role in the process of carcinogenesis and phytochemicals have anti-inflammatory properties gaining more importance in cancer chemoprevention. The present study aimed to investigate the anti-inflammatory effect of allyl isothiocyanate (AITC) on 7,12-dimethylbenz(a)anthracene (DMBA)- and N-methyl-N-nitrosourea (MNU)-induced mammary carcinogenesis in female Sprague–Dawley rats.

Allyl isothiocyanate, a potent chemopreventive agent targets AhR/Nrf2 signaling pathway in chemically induced mammary carcinogenesis

Abstract: In the present study, we investigated the effect of allyl isothiocyanate (AITC) on liver detoxification signaling pathway in 7,12-dimethylbenz(a)anthracene (DMBA)-induced mammary carcinogenesis. Mammary tumor was induced by a single dose of DMBA (25 mg/rat) injected subcutaneously near the mammary gland in Sprague-Dawley rats. DMBA-alone-treated rats show an increased synthesis of phase I detoxification enzymes, lipid peroxidative markers, liver marker enzymes, and lipid profiles whereas, depletion of phase II detoxification enzymes and antioxidants in rat liver tissues. Oral administration of AITC restored the levels of biochemical markers in DMBA-treated rats. Furthermore, histopathological results also confirmed that AITC protects DMBA-mediated hepatocellular damage. We also observed that AITC treatment significantly downregulates AhR and upregulates the expression of Nrf2 in DMBA-treated rats. The binding efficacy of AITC with AhR and Nrf2 analysis by molecular docking studies reveals that AITC has strong interaction with AhR and Nrf2 proteins through hydrogen and hydrophobic interactions. Thus, AITC prevents DMBA-induced mammary carcinogenesis via inhibition of phase I and induction of phase II detoxification enzymes by modulating AhR/Nrf2 signaling pathway.

Tumor Preventive Efficacy of Emodin in 7,12-Dimethylbenz[a]Anthracene-Induced Oral Carcinogenesis: a Histopathological and Biochemical Approach

Abstract: The aim of the present study is to focus the chemopreventive potential of Emodin during 7,12-dimethylbenz[a]anthracene (DMBA) induced hamster buccal pouch carcinogenesis. Tumors were developed in the buccal pouches of golden Syrian hamsters by painting with 0.5% DMBA thrice a week for 14 weeks. The status of lipid peroxidation, antioxidants and detoxification agents were utilized as biochemical endpoints and the expression pattern of apoptotic proteins was employed as molecular endpoints in addition to the histopathological studies, to substantiate the anticancer potential of Emodin. Hamsters treated with DMBA + Emodin revealed mild to moderate precancerous lesions such as hyperplasia and dysplasia whereas 100% tumor formation was noticed in hamsters treated with DMBA alone. Also, Emodin treatment modulated the status of lipid peroxidation, antioxidants, phase I and II detoxification agents and apoptotic proteins in favor of the inhibition/reversal/suppression of the oral tumorigenesis in DMBA treated hamsters. The present study thus concludes that the chemopreventive potential of Emodin relies on its pro-apoptotic and antioxidant efficacy during DMBA induced hamster buccal pouch carcinogenesis.

Chemopreventive potential of vanillic acid against 7,12-dimethylbenz(a)anthracene-induced hamster buccal pouch carcinogenesis.

Abstract: Objectives: The aim of this study was to evaluate the chemopreventive potential of vanillic acid against 7,12-dimethylbenz(a)anthracene (DMBA)-induced hamster buccal pouch oral carcinogenesis. Materials and Methods: Determine the tumor incidence, tumor volume and burden, assessment of the status of Phase I and Phase II detoxification enzymes were measured in the liver and buccal mucosa of hamsters using specific colorimetric methods. Results: One hundred percent tumor formation was observed in DMBA alone treated hamsters. Phase I and Phase II detoxification enzymes status were significantly altered DMBA-induced oral carcinogenesis. Vanillic acid (200 mg/kg bw p.o) significantly restored the biochemical variables of liver and buccal mucosa in DMBA + vanillic acid treated hamsters to near normal range compared with DMBA alone treated hamsters. Conclusion: The present study thus shows chemopreventive potential of vanillic acid in DMBA-induced hamster buccal pouch carcinogenesis. Vanillic acid improves the phase I and phase II detoxification enzymes in DMBA treated hamsters.

Chemopreventive potential of esculetin in 7,12-dimethylbenz(a)anthracene-induced hamster buccal pouch carcinogenesis.

Abstract: 7,12-Dimethylbenz(a)anthracene (DMBA)-induced hamster buccal pouch carcinogenesis is widely preferred to assess the tumor-inhibiting efficacy of the medicinal plants or their constituents The present study explores the tumor-inhibiting potential of esculetin by utilizing the status of lipid peroxidation by products (thiobarbituric acid reactive substances), antioxidants (vitamin E, reduced glutathione, superoxide dismutase, catalase, and glutathione peroxidase), and phase I and phase II detoxification agents as biochemical end points and by using histopathological studies as well in DMBA-induced hamster buccal pouch carcinogenesis Oral tumors developed in the buccal pouch were subjected to histopathological studies, and were confirmed as oral squamous cell carcinoma Hamsters treated with DMBA alone showed an abnormal pattern of lipid peroxidation, antioxidants, and detoxification agents as compared to control hamsters The status of the above-mentioned biochemical markers and histopathological abnormalities were found to be reversed in DMBA + esculetin-treated hamsters The result of the present study thus indicates the tumor preventive potential of esculetin in DMBA-induced oral carcinogenesis

Parthenolide attenuates 7,12-dimethylbenz[a]anthracene induced hamster buccal pouch carcinogenesis.

Abstract: Over the decades, the survival rates for oral cancer have not improved despite development in novel diagnostic and therapeutic strategies. Therefore, the present study is aimed at investigating the chemopreventive potential of parthenolide in DMBA-induced hamster buccal pouch carcinogenesis. The hamsters were divided into 4 groups (n = 6/group). Group I was treated as control. Groups II and III were painted with a solution of 0.5% DMBA three times per week for 14 weeks on the left buccal pouches. In addition, group III were orally administrated with parthenolide 2 mg/kg b.w on days alternate to the DMBA application. Group IV received only parthenolide. At the end of 14th week all hamsters were sacrificed. Buccal tissues from all hamsters were evaluated for histopathology. Biochemical studies were carried out using plasma, liver, and buccal mucosa of control and experimental hamsters. Gene and protein expression studies of apoptotic markers p53, Bcl-2, and Bax were performed. The results showed 100% tumor formation and marked alterations in histopathology, status of detoxification enzymes, lipid peroxidation, and antioxidant profile in group II hamsters. Oral administration of parthenolide completely prevented tumor formation and significantly reduced the severity of histopathological changes in group III hamsters. The status of detoxification enzymes, lipid peroxidation, and antioxidants were significantly restored in parthenolide treated group compared to group II hamsters. The apoptotic gene p53 and antiapoptotic gene Bcl-2 were significantly down regulated; whereas, pro-apoptotic gene Bax was up regulated in group III hamsters compared to group II. The results of the present study suggest that parthenolide have potent chemopreventive, antioxidant, and apoptotic effect in DMBA-induced oral carcinogenesis.

Differential signaling pathway activation in 7,12-dimethylbenz[a] anthracene (DMBA)-treated mammary stem/progenitor cells from species with varying mammary cancer incidence.

Abstract: A natural variation exists in the susceptibility to mammary cancer among wild and domestic mammalian species. Mammary stem/progenitor cells (MaSC) represent a primary target cell for transformation; however, little is known about the intrinsic response of these cells to carcinogenic insults. Polycyclic aromatic hydrocarbons (PAH), such as 7,12-dimethylbenz[a]anthracene (DMBA), are abundantly present in the environment and have been linked to the development of mammary cancer in humans and rodents. We treated MaSC from equine (mammary cancer-resistant) and canine (mammary cancer-susceptible) species with DMBA and assessed cytochrome P450 metabolic activity, DNA damage and viability. Our notable findings were that MaSC from both species showed DNA damage following DMBA treatment; however, equine MaSC initiated cell death whereas canine MaSC repaired this DNA damage. Follow-up studies, based on genome-wide transcriptome analyses, revealed that DMBA induced activation of both the intrinsic and extrinsic apoptotic pathways in equine, but not canine, MaSC. Based on these findings, we propose a hypothetical model in which undergoing apoptosis in response to an oncogenic event might contribute to a lower incidence of mammary cancer in certain mammalian species. Such a mechanism would allow for the elimination of DNA-damaged MaSC, and hence, reduce the risk of potential tumor-initiating mutations in these cells.

The effect of Ficus carica latex on 7, 12-dimethylbenz (a) anthracene-induced breast cancer in rats.

Abstract: Objective: In traditional medicine, Ficus carica (also known as fig) latex is recognized as a remedy with various therapeutic effects. Recently, in vitro studies have reported the anticancer effect of this latex on cancer cell lines. This study evaluated the effect of this latex on breast cancer growth, hematological parameters, and histopathology in rats. Materials and Methods: Twenty-four female rats were randomly divided into 3 groups. In cancerous group, 0.5 ml 7, 12-dimethylbenz (a) anthracene was injected to nipple for breast cancer induction. The control group received sesame oil at the same volume through similar route. In fig latex treated group (Fle), breast cancer was induced and then 0.5 ml of fig latex was intratumorally injected on a daily basis for 4 weeks. Tumor size was measured at the 2nd, 4th and 6th weeks of the experiment. Blood samples were used for investigation of the hematological parameters and livers, kidneys and tumor tissues were removed for histopathological analysis. Results: The tumor size in Fle group was significantly decreased compared to the cancerous group. Haematocrit, hemoglobin, RBC and their indices were significantly decreased, whereas platelet, leukocyte and white blood cell numbers were significantly increased in cancerous group compared to the control group. There were no changes in these parameters in the Fle group compared to the control group. There were severe pathological changes in the livers and kidneys of cancerous group, but not in Fle group. Conclusion: These results suggest that fig latex could decrease tumor growth without having any adverse effect on hematological and histological factors. However, further investigation is required in this field.

Taxifolin possesses anti-cancer activity on the 7,12-Dimethylbenz(a)anthracene-Induced breast cancer in the sprague dawley rats by remodeling nuclear factor Erythroid 2- Kelch-Like ECH-Associated Protein 1-Heme Oxygenase 1 and anti-oxidant pathways

Abstract: Background: In mammary cancer, alterations in various gene expressions and signaling pathways occurs due to the secondary effects of oxidative stress that facilitates cancer by causing genomic instability and mutagenic alterations. Several phenolic compounds are active against various malignancies. Taxifolin (TAX) exhibits diverse bioactivity profile that also contributes toward its anticancer efficacy. Objective: The present study has been designed for estimation of the anticancer potential of TAX on 7,12-dimethylbenz(a)anthracene (DMBA)-induced breast cancer in Sprague Dawley (SD) rats. Materials and Methods: Molecular docking analysis of Kelch-like ECH-associated protein 1 (Keap-1) and heme oxygenase-1 (HO-1) was carried out using Maestro tool to rationalize the activity of TAX based on their binding potential. This was followed by DMBA administration in air pouch to induce mammary cancer in female SD rats (50–55 days old). After 90 days of cancer induction, the chemotherapeutic potential of TAX was evaluated by the administration of TAX at doses 10, 20, and 40 mg/kg/day. Besides this, the effect of TAX on Keap-1-nuclear factor erythroid-2 (Nrf-2) pathway associated with HO-1 and NADPH:quinoneoxidoreductase 1 (NQO1) expressions and their effect on the anti-oxidative and anti-proliferative activity was also evaluated through immunofluorescence analysis, real-time quantitative polymerase chain reaction, and biochemical estimations. Results: TAX revealed protective effect against lipid peroxidation, enzymatic (superoxide dismutase [SOD], manganese-containing SOD, copper- and zinc-containing SOD, catalase, and glutathione peroxidase), and nonenzymatic (reduced glutathione, α-tocopherol, and ascorbic acid) anti-oxidative markers in serum, liver, kidney, and breast tissue of both control and experimental groups. The study revealed upregulation of protective Nrf-2, HO-1, and NQO1 expressions with consequent suppression in Keap-1 mRNA expression. Conclusion: This study revealed the potency of TAX in the inhibition of mammary carcinogenesis through Nrf-2-Keap-1-HO-1 and antioxidant pathway. Abbreviations used: RT-qPCR: Real-time quantitative polymerase chain reaction; ODC: Ornithin decarboxylase; HO-1; Heme oxygenase-1; PAHs: Polyaromatic hydrocarbons; TBARS: Thiobarbituric acid reactive species; NQO1: NADPH:quinoneoxidoreductase 1; Keap-1: Kelch-like ECH associated protein 1; Nrf2: Nuclear factor erythroid 2; SD: Sprague Dawley.

Protective Effect of Allyl Isothiocyanate on Glycoprotein Components in 7,12-dimethylbenz(a)anthracene Induced Mammary Carcinoma in Rats.

Abstract: The present study aimed to investigate the protective effect of allyl isothiocyanate (AITC) on glycoprotein components in 7,12-dimethylbenz(a)anthracene (DMBA) induced mammary carcinogenesis in female Sprague–Dawley rats. Mammary tumor was induced by a single dose of DMBA (25 mg/rat) injected subcutaneously near mammary gland. The levels of glycoprotein components such as hexose, hexosamine and sialic acid were analyzed colorimetrically in plasma, mammary and liver tissues. We observed an increased levels of glycoprotein components in plasma, mammary and liver tissues in cancer bearing rats. It was further confirmed by Periodic Acid Schiff staining in mammary and liver tissues. Upon oral administration of AITC to DMBA injected rats, the abnormal changes were reverted back to near normal levels and biochemical findings are supported by histological analysis. This could be due to the anti-neoplastic potential of AITC against DMBA-induced mammary carcinogenesis. The result shows that AITC has the potential to inhibit abnormal glycosylation that favors neoplastic transformation.

Evaluation of the chemopreventive effects of Ankaferd Bloodstopper in 7,12-dimethylbenz[a]anthracene-induced oral epithelial dysplasia

Abstract: Ankaferd BloodStopper® (ABS) is an herbal extract which has been used historically as a hemostatic agent in traditional Turkish medicine. ABS comprises of standardized mixture of herbs Thymus vulgaris, Glycyrrhiza glabra, Vitis vinifera, Alpinia officinarum, and Urtica dioica. In addition to its hemostatic effects, the herb ABS contains some other biological effects including antioxidant and antitumoral properties. The aim of this study is to investigate the chemopreventive effects of ABS in 7,12-dimethylbenz[a]anthracene (DMBA)-induced oral epithelial dysplasia. A total of 40 Sprague Dawley rats were randomly divided into four groups. Group 1 animals received DMBA alone, and group 2 animals received both DMBA and Ankaferd. Group 3 animals received ABS alone while group 4 animals served as control group and received only liquid paraffine. All animals were sacrificed, and tissue samples were analyzed histologically at the end of the experimental period (14 weeks). Histological studies have shown that the buccal pouches of animals treated with DMBA alone revealed severe dysplasia while only mild or no dysplasia were noticed in DMBA + ABS group. Ankaferd were administered to animals and control group showed no dysplasia or other oral lesions. The results suggest that Ankaferd Bloodstopper® has chemopreventive effect against DMBA-induced oral epithelial dysplasia. Ankaferd Bloodstopper® could be used as a supportive treatment option of cancer in oral and maxillofacial surgery since it possesses chemopreventive effect.

Dampness-Heat Accelerates DMBA-Induced Mammary Tumors in Rats

Abstract: 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.

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.

Abstract: 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.

Cetirizine and thalidomide synergistically inhibit mammary tumorigenesis and angiogenesis in 7,12-dimethylbenz(a)anthracene-treated rats.

Abstract: OBJECTIVE Cetirizine (CET) and thalidomide (THA) have been previously found to influence angiogenesis. The present study aimed to assess the ability of these drugs to influence mammary carcinogenesis in rats. MATERIALS AND METHODS Sixty Sprague-Dawley female rats, aged 8 weeks, received 15 mg of 7,12-dimethylbenz(a)anthracene (DMBA) intragastrically. CET and THA (1.0 and 3.0 mg/kg, respectively) were administered orally for 118 days after DMBA administration. At the end of the treatment period, mammary tumors were counted and weighed, and their morphology was analyzed using light microscopy. In tumor tissue, proliferation and apoptotic indices and microvessel density were determined using immunohistochemical techniques; the levels of angiogenic factors, vascular endothelial growth factor and basic fibroblast growth factor, were measured by western blotting. RESULTS CET and THA, administered separately, failed to influence tumor formation and angiogenesis. In contrast, the drug combination decreased latency to first tumor (significant difference from vehicle-treated control and groups that received either drug alone, P<0.01) and significantly lowered tumor number per rat, number of malignant tumors per rat, tumor burden, and tumor number per tumor-bearing animal (P<0.05 or <0.01). In tissue of malignant tumors, the drug combination decreased the number of proliferating cells, microvessel density, and levels of vascular endothelial growth factor and basic fibroblast growth factor and stimulated apoptosis (difference from all other groups, P<0.01). CONCLUSION It was shown for the first time that H1-antagonist and THA synergistically inhibit DMBA-induced mammary carcinogenesis; this effect was associated with a decrease in tumor angiogenesis. Further study of the anticancer and antiangiogenic activity of the combination may provide a new approach to breast cancer treatment.

Hesperetin on Cell Surface Glycoconjugates Abnormalities and Immunohistochemical Staining with Cytokeratin in 7,12 Dimethylbenz(a)anthracene Induced Hamster Buccal Pouch Carcinogenesis

Abstract: Hesperetin, a naturally occurring citrus flavanone of the bioactive substance, possesses different pharmacological and biochemical activities including anti-cancer and anti-oxidants effect. The aim of the study to investigate that hesperetin on abnormalities of glycoconjugates (protein bound hexose, hexosamine, total sialic acid and fucose), histology (PAS staining) and immunoexpression of cytokeratin during 7,12-dimethylbenz(a)anthracene (DMBA) induced hamster buccal pouch (HBP) carcinogenesis. Oral tumors were developed in the buccal pouches of male golden Syrian hamsters by topical application of 0.5% DMBA thrice a week for 10 weeks and developed morphological alterations depicted as hyperplasia, dysplasia and well-differentiated squamous cell carcinoma formation with noticeable abnormalities of glycoconjugates and cytokeratin. The protective effect of hesperetin against DMBA was evaluated by assessing immunohistochemical expression, histological sections of buccal tissues and the levels of glycoconjugates in the buccal mucosa and plasma were analyzed. Hesperetin administrated orally at a dose of 20 mg/kg b.w. to hamsters treated with DMBA, significantly reduced the status of glycoconjugates and cytokeratin to the near normal range. Overall findings accomplished that hesperetin protects cell surface glycoconjugates abnormalities in DMBA induced HBP carcinogenesis.

Retinoic acid‑metabolizing enzyme cytochrome P450 26A1 promotes skin carcinogenesis induced by 7,12‑dimethylbenz[a]anthracene

Abstract: Elevated expression of the retinoic acid-metabolizing enzyme cytochrome P450 26A1 (CYP26A1) has been demonstrated to have an oncogenic function in carcinogenesis. In order to address the oncogenic capacity of CYP26A1 in vivo, transgenic mice that ubiquitously overexpressed CYP26A1 driven by the cytomegalovirus promoter were generated in the present study. Since the growth of these animals was normal for ≤15 months and they presented no evident abnormalities, a two-stage skin carcinogenesis analysis was performed. In the CYP26A1 transgenic mice, papilloma formation was observed within 7 weeks after administration of the carcinogen 7,12-dimethylbenz[a]anthracene (DMBA). Development of papillomas in these animals was significantly accelerated when compared with that observed in the control mice following treatment with DMBA in combination with the chemical tumor promoter 12-O-tetradecanoylphorbol-13-acetate. In addition, constitutive expression of CYP26A1 increased the susceptibility of these mice to the generation of squamous cell carcinomas caused by treatment with the carcinogen alone. It is thus concluded that CYP26A1 expression promotes skin carcinogenesis initiated by DMBA.

Inhibitory Effect of Honey on 7,12-Dimethylbenz(a)anthracene- Initiated and Croton Oil-Promoted Skin Carcinogenesis

Abstract: Background: Honey as a natural product exhibits a variety of biological and pharmacological activities Its anti-inflammatory, antioxidant, antibacterial, and antihypertensive effects have already been proven Objectives: In this study, the inhibitory effects of honey on the 7,12-dimethylbenz(a)anthracene-initiated and croton oil-promoted mice skin carcinogenesis were studied Methods: Albino Swiss mice were pretreated with multiple topical applications of honey After nine hours, the carcinogenesis was initiated by a single dose of DMBA Topical croton oil, as for a promoting agent, was applied biweekly for a period of 30 weeks Results: The tumor incidences were observed Compared to the control group, the honey pre-treated mice showed a significant inhibition in tumor incidences In addition, the enhanced uptake of [3H]-thymidine in mice skin DNA was inhibited in honey-pretreated animals as compared to the control group Conclusions: Taken together, the results suggest that the antioxidants existed in honey have diminishing effects on croton oilmediated murine skin tumor promotion In conclusion, we suggest that honey as an effective natural preventive agent may provide protection against skin cancer