DMBA Application Research Articles

Evaluation of In-vivo Anticancer Activity Choerospondias axillaris in Swiss Albino Mice Models

Background and Objective: The fruits of the plant, Choerospondias axillaris are one of the richest sources of flavonoids phenol and vitamin C that have been shown to possess a variety of biological activities. The present study was aimed to study the potential anti-cancer activity of the methanolic extract of fruit of Choerospondias axillaris using the in-vivo model to scientifically validate the folkloric use of the Choerospondias axillaris.
 Study Design: In-vivo model.
 Place and Duration of the Study: Department of pharmacology, Karnataka College of pharmacy, Bangalore India, between October 2021 to June 2022.
 Methods: Anti-cancer property of Choerospondias axillaris was evaluated against DMBA/croton oil induced skin tumorigenesis in Swiss albino mice. A single topical application of DMBA (100g/100l of acetone), followed 2 weeks later by repeated application of croton oil (1% in acetone three times a week) for 16 weeks. In contrast, animals treated orally with Choerospondias axillaris 200mg/kg/b.w. (group IV) and orally with Choerospondias axillaris 400mg/kg/b.w. (group V) and 5 Flu 10mg/kg (group III). The following parameters like; body weight, tumor incidence, cumulative number of tumors, tumor yield, average latency period, number of papillomas, haematological parameters, Serum Zinc and C-Reactive Protein, anti-oxidants enzyme, pro-inflammatory cytokines & Histopathological of Tumor skin studies were observed.
 Results: 100 percent tumor incidence exhibited in group II (DMBA/croton oil) whereas the group IV (Choerospondias axillaris 200mg/kg) and group V (Choerospondias axillaris 400mg/kg) and group III (5 Flu 10mg/kg) exhibited 50, 33.7 and 42.5% tumor incidence, which significantly lesser when compared to than group II (Toxic control). The cumulative number of papillomas during the observation period of 16 weeks was significantly decreased in the Choerospondias axillaris treated groups IV, V and III (9, 4 and 6 no’s tumor respectively) in comparison to 18 cumulative numbers of papillomas in carcinogen control group. The average latent period significantly increased in the Toxic control group to 3.2, 4.3, 6.5 and 5.4 in group II, IV, V and III respectively. Tumor yield were significantly lesser (1.5, 0.66 and 1.0) as compared to DMBA/Croton oil treated control. Furthermore, the level of LPO was significantly increased whereas, the activity of CAT level were significantly decreased in skin tissue of DMBA/Croton oil treated animals compared Choerospondias axillaris treated animals. Similarly, NLR (< 3.0), ESR, Serum Zinc and CRP have got improved in treated with Choerospondias axillaris. Protein expression of TGF-beta, IFN-G, TNF-alpha and IL-6 have shown Improvement in markers indicating a reduction in inflammation and immune imbalance in treated with Choerospondias axillaris compared with DMBA/Croton oil where shown moderate immune suppression.
 Conclusion: Based on the results it can be concluded that the test drug Choerospondias axillaris could be a potential candidate for the treatment of skin cancer.

Chemopreventive and therapeutic efficacy of thymoquinone on experimentally induced hamster buccal pouch carcinogenesis

Aim: The present study aimed to investigate the chemopreventive and therapeutic effect of thymoquinone (TQ) on experimentally induced hamster buccal pouch carcinogenesis. Methodology : 40 Syrian male hamsters were classified into 4 equal groups (G(s)) of 10 each. GI: The animals remained untreated. The pouches of animals in GII, GIII, and GIV were painted 3 times a week for 14 weeks (ws). with 7,12-dimethylbenz (a) anthracene (DMBA). GII: No additional treatment was administered. Those in GIII: oral administration of TQ at a dose of 30 mg kg-1, one week before, as well as, during the application of DMBA on alternate days for 14 ws, whereas in GIV: The animals were injected intraperitoneally (IP) with TQ 50 mg/kg body weight thrice a week for 3ws. After the end of the experiment, the gross observations were made. Then, the fresh pouch specimens were surgically bisected into two pieces, one for Hematoxylin and Eosin (H&E) stain and immunohistochemistry (IHC) stain using Bcl-2. The other piece was used for apoptosis detection through a flow cytometry (FCM) test. Results: Gross observation showed variation in reduction of the tumor size in chemoprevention and treated group compared to the DMBA treated group.

The Apoptotic and Antiproliferative Effects of Capsaicin in the Developmental Stages of Oral Squamous Cell Carcinoma Induced in Hamsters.

Background and aimSeveral epidemiological and experimental studies have approve that the vegetarian diet has an anticancer effect. Capsaicin is the active botanical ingredient found in red chili peppers. While the data strongly argue for the significant anticancer benefits of capsaicin, nevertheless, much information is required to shed light on the anticancer molecular mechanisms to improve knowledge and suggest potential therapeutic mechanisms for the use of capsaicin against cancer. This study aimed to investigate the effect of capsaicin on the rate of cell division and apoptosis in the development of oral squamous cell carcinoma induced in the buccal pouch of hamsters.Materials and methodsThe sample consisted of two groups; the first group consisted of 20 hamsters with the application of carcinogenic 7,12-dimethylbenz(a)anthracene (DMBA) in the buccal pouch (the control group) and the second group (the study group) also consisted of 20 hamsters with the application of DMBA in alternatively with capsaicin. Tissue biopsies were taken from experimental animals after sacrificing. The samples were immunostained for the detection of Ki-67 and Bcl-2 proteins.ResultsImmunohistochemical staining by monoclonal antibody to Ki-67 and Bcl-2 in the study group showed lower expression at all stages of oral cancer development compared with their expression in the control group. After performing the one-way (ANOVA) test, we found statistically significant differences by comparing the expression degree of Ki-67 and Bcl-2 proteins in both study groups, where the p-value was less than 0.05.ConclusionWe conclude from the data of our study that capsaicin has an anti-cancer role in oral squamous cell carcinoma if applied in the digestive tract of experimental animals by inhibiting the proliferation of cancer cells and activating apoptosis in them.

Pomegranate molasses and red grape vinegar: can they alleviate dysplastic changes in chemically induced oral squamous cell carcinoma in hamsters?

76 male hamsters were divided equally into 4 groups (19 each). Group I served as control group with no intervention. Group II received topical application of 0.5% 7, 12-dimethylbenz[a]anthracene (DMBA) on the left buccal pouches for 16week with no intervention. Group III received a 0.5ml of Pomegranate molasses plus 0.5 ml distilled water through ingestion daily concomitant with DMBA application and continued for 3 months post induction period. Group IV received a red grape vinegar in a protocol similar to group III. Then the pouches were collected fixed and processed for H&E, anti-TGF-β and anti-CK-19 staining. Results: group II showed classical dysplastic changes with statistically significant higher expression of anti-TGF-β and CK-19 (P<0.0001) compared to group III and IV. The later showed reduction of dysplastic changes and anti-TGF-β and CK-19 expression. There was no significant difference between the two treatment modalities. Conclusion: Both pomegranate molasses and red grape vinegar reduced the signs of dysplasia via reduction of TGF-β and CK-19 expression and consequently reduction of the EMT. Both pomegranate molassess and red grape vinegar represent a promising protective therapeutic modality for reduction of dysplastia and carcinogenesis.

Assessment of Chemoprotective Potential of Curcumin against DMBA-Croton Oil Induced Skin Cancer in Mice

Background: Skin cancer is the most aggressive form of cancer with a high mortality rate. Different medications of skin cancer are accessible, yet because of improvement of multi-drug resistance, flow and rising chemotherapies have a generally low achievement rate. This emphasize the importance of discovering new compounds that are both safe and effective against skin cancer. This study used and compared different routes of administration of a natural compound curcumin to investigate the anti-cancer effect.&#x0D; In this investigation it has been resolved that the curcumin expands CAT and SOD levels alongside decline in the TBARS levels.&#x0D; Methods: The hindrance of tumour rate Curcumin was assessed in mice on two phase procedure of skin carcinogenesis incited by single utilization of DMBA/7,12-Dimethylbenz[a]-anthracene (100 µg/100 µl of CH3)2CO), and after 2 weeks advanced by rehashed use of croton oil (1% CH3)2CO/thrice in seven days) till the finish of the trial (i.e. 16 weeks). Oral administration of drug at a dose of 500 mg/kg body weight/day at the pre-initiation stage (i.e. 7 days prior and 7 days after DMBA application), promotional stage (for example from the time of croton oil application) and at both the stages (i.e. 7 days before DMBA application and proceeded till the finish of investigation) to the mice Treatment were started 1 week before the exposure to the carcinogen and continued till 25 weeks daily. At the end of experimental period all the animals were sacrificed and observed for various parameters.&#x0D; Results: The following parameters (body weight, biochemical studies, haematological studies) were observed and data was collected time to time and calculated statistically to evaluate the anticancer effect of curcumin was found to effective against the skin cancer.

Chemopreventive effect of olive oil in experimentally induced hamster buccal pouch epithelial dysplasia (Randomized control trial)

The progression of tumor depends on the level of Bcl-2 which protects the cells from undergoing apoptosis, and its level should be more than the level of the death inducer. So, our Aim: To investigate chemopreventive effect of olive oil in epithelial alteration which induced in hamster buccal pouch. Methods: Epithelial dysplasia will occur by the application of DMBA on alternative days for 8 weeks on hamster buccal pouch. Hematoxylin and Eosin (H&E) and Streptavidin-biotin immunoperoxidase staining techniques were used to detect the expression of Bcl-2 in three groups (G1 negative control or normal group, G2 DMBA group and G3 olive oil chemoprevention group). Evaluation of the immunostaining was done by using computer image analyzer system. Results: H & E stained histological section in G1 with normal mucosa of HBP intact, and continuous epithelium of thin keratinized stratified squamous epithelium while in G2 there were incidence of severe epithelial dysplasia with hyperkeratosis & G3 reduced dysplasia incidence and severity as compared to G2. Bcl-2 immunohistochemical expression in G1 in basal & suprabasal layers while in G2 & G3 located in all epithelial layers with statistically highly significant difference (P G1, G3) and (G3>G1). Conclusion: Olive oil plays an important role in reduction and prevention of transformation of normal oral epithelium into epithelial dysplasia. The liquid form of olive oil may be considered as a new line of chemoprevention in oral dysplasia and the Bcl-2 expression evidenced this reduction of abnormality in epithelial dysplasia.

Chemopreventive effect of hesperidin, a citrus bioflavonoid in two stage skin carcinogenesis in Swiss albino mice

The cancer-protective ability of hesperidin was investigated on 7, 12-dimethylbenz[a]anthracene (DMBA) and 12-O-tetradecanoyl phorbol-13-acetate (TPA)-induced skin carcinogenesis in Swiss albino mice. Topical application of DMBA+TPA on mice skin led to 100% tumour incidence and rise in average number of tumours. Administration of different doses of hesperidin (HPD) before (pre) or after (post) and continuous (pre and post) DMBA application significantly reduced tumour incidence and average number of tumours in comparison to DMBA+TPA treatment alone. Topical application of DMBA+TPA increased oxidative stress as shown by significantly increased TBARS values and reduced glutathione contents, and glutathione-S-transferase, superoxide dismutase and catalase activities. Hesperidin treatment significantly reduced TBARS values and elevated glutathione concentration and glutathione-S-transferase, superoxide dismutase and catalase activities in the skin/tumors of mice treated with HPD+DMBA+TPA, HPD+DMBA+TPA+HPD or DMBA+TPA+HPD when compared to DMBA+TPA application alone. The study of molecular mechanisms showed that hesperidin suppressed expression of Rassf7, Nrf2, PARP and NF-κB in a dose dependent manner with a maximum inhibition at the level of 300 mg/kg body weight hesperidin. In conclusion, oral administration of hesperidin protected mice against chemical carcinogenesis by increasing antioxidant status, reducing DMBA+TPA induced lipid peroxidation and inflammatory response, and repressing of Rassf7, Nrf2, PARP and NF-κB levels.

Calcium Fructoborate Prevents Skin Cancer Development in Balb-c Mice.

Tumor microenvironment, genetic, and non-genetic factors are responsible for the atypical metabolic feature of cancer cells. Aberrant activity of PI3K/Akt pathway, increased glycolytic flux, and decreased intracellular pH gradient are the leading causes of this feature. Calcium Fructoborate (CaFB), a sugar-borate ester, has major benefits for human health. The aim of this study was to explore the implication of CaFB on experimentally induced skin cancer in vivo. According to the treatment, 92 female Balb-c mice are divided into six groups: control, CaFB (3mg/kg/day), 7,12-Dimethylbenz(a)anthracene (DMBA)+12-O-tetradecanoylphorbol-13-acetate (TPA) (97.5nmol DMBA, 6.5nmol TPA), T1: CaFB+DMBA+TPA (3mg/kg/day CaFB together with DMBA), T2: DMBA+CaFB+TPA (3mg/kg/day CaFB together with TPA), T3: DMBA+TPA+CaFB (3mg/kg/day CaFB after tumor formation). Topical DMBA and TPA application resulted in a significant increase in the protein levels, immunoreactivity, and mRNA expression of HRAS, HIF1α, Akt, and PTEN (p < 0.05). Moreover, an increase in the number of TUNEL-positive cells was observed in DMBA-TPA group compared with the control group (p < 0.05). CaFB application reduced the protein levels, immunoreactivity, and mRNA expressions of HRAS, HIF1α, Akt, and PTEN and also decreased the number of TUNEL-positive cells. Recent evidence obtained from our study validated that CaFB treatment may have skin cancer-preventing effect.

Protective Effects of Grape Molasses and Resveratrol Against DMBA Induced Oxidative Stress in Rat Ovarian Tissues

Objective: The polyphenolic compound, resveratrol (3, 4’, 5-trihydroxystilbene), trans-resveratrol is a natural phytoalexin that exists in many different foods such as grape peel and seed, peanut, mulberry and blueberry. Molasses is a natural food obtained by boiling and concentrating fruit juices known to be rich in minerals such as iron, phosphorus, potassium, sodium, calcium and magnesium, and phosphoric acid, formic acid, organic acids and some vitamins. Polyphenolic compounds are natural antioxidants and are known to have protective effects against tissue damage caused by reactive oxygen species (ROS). In this study, we aimed to investigate the protective effects of grape molasses and resveratrol on ovarian damage induced by 7, 12-dimethylbenz [a] anthracene (DMBA). Methods: A total of 42 old female Wistar Albino rats, aged 18 weeks were divided into six groups. 10 mg/kg DMBA was injected in the rats in DMBA group subcutaneously on day 0 and day 7 while grape molasses feed with 20% grape molasses was given along with DMBA application to the rats in DMBA + grape molasses group. Resveratrol was administered by subcutaneous injection at 10 mg/kg/day to the DMBA + Resveratrol group, while only feed with 20% grape molasses was given to the grape molasses group. Resveratrol was administered by subcutaneous injection at 10 mg/kg/day to the resveratrol group. Results: GSH activity between the control group and molasses group, DMBA and DMBA + molasses groups and the control group and the DMBA + grape molasses groups was found statistically significant. Regarding the NO activity, the difference between the DMBA and resveratrol groups, DMBA and DMBA + resveratrol groups and the grape molasses and resveratrol groups was found statistically significant. MDA activity between DMBA + resveratrol and DMBA + grape molasses groups, and DMBA + grape molasses and grape molasses groups was found statistically significant. Conclusion: Molasses as one of the most important nutrient sources of Eastern and Central Anatolia was observed to decrease ovarian tissue oxidative damage induced with DMBA compared to resveratrol.

A NATURAL PRODUCT DECURSIN ENHANCES THE RADIOSENSITIZATION OF IONIZING RADIATION AGAINST DMBA-INDUCED TUMOR

Objective: Radiation therapy has gained significant attention for the treatment and prevention of solid and malignant human tumors. However, after periodical exposures, radiation therapy losses its efficacy against cancer cells displaying radio-resistant phenotypes. Therefore, decursin might improve the efficiency of radiotherapy against a variety of human cancers.&#x0D; Methods: The chemopreventive efficacy of decursin was evaluated against B16F10 cancer cell lines and DMBA/croton oil-induced skin carcinogenesis in BALB/c mice. Decursin was administered intraperitoneal at the dose of 20 mg/kg/day for 8 weeks following exposure to 5 Gy of ionizing radiation (IR) after 1 month of DMBA application. Western blot was performed for underlying mechanism of radioresistance.&#x0D; Results: Decursin suppressed the proliferation and viability of melanoma cancer cell lines in a concentration- and time-dependent manner. The in vivo data collected from mice model revealed that decursin reduced the precancerous skin lesions and the incidence of tumor bearing in radiation-exposed mice. Decursin also enhanced the effect of IR by downregulation of Akt/NFκB pathway through activation of IκBα.&#x0D; Conclusion: Our results suggest that the activation of Akt/NFκB establishes a pro-survival response to radiation that may account for the development of radioresistance. Decursin blocks the abnormal expression of these proteins and potentiates the radiotherapeutic effect.

Antioxidant effect of grape molasses in rat heart tissues

Grape molasses, which is rich in mineral substances such as flavonoids, polyphenol, antioxidants, iron, calcium, phosphorus, potassium, and magnesium is a natural nutrient, that is concentrated with boiling without adding any additive. In this study, we aimed to investigate the effects of molasses and resveratrol diets on oxidative stress parameters in cardiac damage induced with 7,12-dimethylbenz(a)anthracene (DMBA). A total of 42 Wistar albino female rats were divided into six groups with seven in each. Control group was administered subcutaneous injection of 1 mL mixture including 20 mL sesame oil + 30 mL Dimethyl Sulphoxyde (DMSO); DMBA group received subcutaneous injection of 10 mg/Kg DMBA on the 0th and 7th days. DMBA + Molasses group received DMBA application and feed containing 20 % molasses; DMBA + Resveratrol group received subcutaneous injection of DMBA + 10 mg/Kg resveratrol a day. Molasses group received feed with 20 % molasses, and Resveratrol group received subcutaneous injection of 10 mg/Kg resveratrol a day. There was a statistically significant difference between the DMBA group and DMBA + Molasses, control, resveratrol and molasses groups in terms of nitric oxide activity. There was a statistically significant difference between the DMBA group and DMBA + Resveratrol, DMBA + Molasses, control, molasses and resveratrol groups in term of malondialdehyde (MDA) activity. There was a statistically significant difference between DMBA groups, and DMBA + Molasses, DMBA + Resveratrol, and control groups in terms of glutathione (GSH) activity. Based on these results, it could be said that grape molasses could provide protection against oxidative stress as resveratrol, decreasing the risk of damage by free radicals.

Chemopreventive efficacy of carvacrol on experimentally induced hamster buccal pouch carcinogenesis

The aim of the present study was directed to investigate the chemopreventive efficacy of carvacrol on experimentally induced hamster buccal pouch(s) (HBP(s) carcinogenesis utilizing Bcl-2 and Bax as apoptotic markers. Material and methods: Fifty five Syrian male hamsters, five weeks old, weighing 80-120 gm. The animals were divided into three groups (G(s)) (GI, GII and GIII): GI (negative control): 5 animals were left untreated. GII: (DMBA painted group): the right BPs of 20 animals were painted with 0.5% DMBA in paraffin oil 3 times a week on alternative days; they were subclassified into two subgroups (GIIA and GIIB). GIIA: the right BPs of 10 hamsters were painted with DMBA for 6 weeks. GIIB: the right buccal pouches of 10 hamsters were painted with DMBA for 14 weeks. GIII (carvacrol chemoprevention group): 30 hamsters were received carvacrol by the oral route using a specific vehicle in a dose of 15mg/kg; they were subclassified into two subgroups (GIIIA and GIIIB). GIIIA: 15 hamsters were given carvacrol one week before, as well as, during DMBA application for 6 weeks. GIIIB: 15 hamsters were given carvacrol one week before, as well as, during DMBA application for 14 weeks. Results: Gross observation revealed that, there is reduction in the size and distribution of tumors in the GIII compared to that observed in GII. Histopathological findings using H&E stain demonstrated variable changes in the GIII ranging from decrease severity to complete absence of dysplastic features compared to those observed in GII. Immunohistochemical (IHC) results of GIII revealed an increased Bax expression and decreased Bcl-2 expression compared to that observed in GII. Conclusion: The incidence of HBP carcinogenesis was prevented and decreased by oral administration of carvacrol with variable degrees, so it might be considered as a promising chemoprevention agent .The positive effect of carvacrol on apoptosis has been realized, as shown by, increased levels of Bax and decreased levels of Bcl-2 expression during carvacrol chemoprevention, in addition to, highly significantly difference of apoptosis between carvacrol chemoprevention group and DMBA painted group. Keywords: HBP carcinogenesis, carvacrol, apoptosis, DMBA.

Omics-based analysis of the impact of cigarette smoke and cessation in mouse liver and kidney following a 6-month exposure

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.

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

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.

Effects of aqueous cinnamon extract on chemically-induced carcinoma of hamster cheek pouch mucosa

This study aimed to investigate the effects of aqueous cinnamon extract (ACE) on 7, 12-Dimethylbenz[a]anthracene (DMBA)-induced oral carcinogenesis in hamster cheek pouch (HCP) mucosa. Sixty male Syrian hamsters were randomly divided into six equal groups. The hamsters of groups I, II and III received no treatment, DMBA and ACE respectively, for 16 weeks. Groups IV and V were handled as group II and concomitantly treated with ACE for the same period and additionally group V received ACE for other 16 weeks after the stoppage of DMBA application. Group VI hamsters were handled as group III and additionally received DMBA for other 16 weeks after the stoppage of ACE supplementation. Hamsters of each group were euthanized according to the experimental schedule. The buccal pouches were and prepared for H&E stain, PAS reagent, CD3 and PDGF immunohistochemical reactivity. All groups showed dysplastic changes with varying degrees except groups I and III. Deep invasive carcinomas were recorded in 90% of the samples of group II, 60% of group IV, 50% of group V and 40% of group VI. From the previous results, it can be concluded that ACE has the potentiality preventing oral cancer initiation better than inhibiting oral cancer progression.

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

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 14weeks on the left buccal pouches. In addition, group III were orally administrated with parthenolide 2mg/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.

EMODIN DOWNREGULATES CELL PROLIFERATION MARKERS DURING DMBA INDUCED ORAL CARCINOGENESIS IN GOLDEN SYRIAN HAMSTERS.

Background:Cell-cycle disruption is the major characteristic features of neoplastic transformation and the status of cell-cycle regulators can thus be utilized to assess the prognostic significance in patients with cancer. The PCNA, cyclin D1, CDK4, CDK6 and survivin expression in the buccal mucosa was utilized to evaluate the Emodin efficacy on abnormal cell proliferation during 7,12-dimethylbenz(a)anthracene (DMBA) induced oral carcinogenesis in golden Syrian hamsters.Materials and methods:Topical application of DMBA, three times a week for 14 weeks, on the hamsters’ buccal pouches developed well differentiated squamous cell carcinoma.Results:Cyclin D1 and PCNA over-expression and up-regulation of CDK4, CDK6 and survivin were noticed in the buccal mucosa of hamsters treated with DMBA alone. Emodin administration (50mg/kg b.w) orally to hamsters treated with DMBA down-regulated the expression of cell proliferation markers in the buccal mucosa.Conclusions:The anti-cell proliferative role of Emodin is owing to its modulating efficacy on cell-cycle markers towards the tumor suppression during DMBA induced oral carcinogenesis.

Chemopreventive Effects of Cocoa Extract Application Towards Expression of Bcl-2 and Mda on Albino Mice Skin Induced by Dmba-Tpa

This research aims to determine the effect of topical cocoa extract application through ekspression of Bcl-2 and MDA on albino mice skin that induced by DMBA-TPA. The research was conducted at Animal Laboratory for application of DMBA, MDA-TPA and cocoa extract and Biomolecular Laboratory of Medical Faculty of Hasanuddin University Makassar as the place of ELISA examination. The method used was animal experimental with pure experimental design to know the role of topical cocoa extract towards the skin of mice which has been given DMBA-TPA three times a week in 12 weeks. The research unit was the skin of the back side of albino mice which have been excised and divided into 5 groups of treatment. The results indicate that extract of concentration cocoa 400 ppm (p&lt;0.05) which is applied every day has the highest effects decreased of Bcl-2 and MDA expression after being inducted by DMBA-TPA three times a week.

Protective Effect of Cocoa Seeds Extract Application on PCNA Expression in Albino Mice Receiving DMBA Exposure

Skin cancer incidence is directly proportional to malignancies in other organs and represents a health problem. This study aims to evaluate the protective effect of topical cocoa extract application on PCNA expression in mice receiving DMBA exposure. This study was conducted in Animal Laboratory for DMBA administration and cocoa extract application, Bimolecular Laboratory of Hasanuddin University as the location of ELISA evaluation. The study used animal experimental method with pure experimental design to find out the role of topical cocoa seeds extract on the skin of mice receiving DMBA application in one week. Twenty mice were divided into 4 treatment groups: first group was control without skin protector, second group with ethanol application, third group with topical cocoa extract application 400 ppm, and fourth group was treated with 800 ppm topical cocoa with 100 ug DMBA exposure three times per week. After one week the treatment was terminated and skin biopsy was excised for PCNA expression evaluation using ELISA. Study findings indicate that 400 ppm and 800 ppm topical cocoa extract had a protective effect on PCNA expression with 400 ppm as the most effective dose.

Solanum trilobatum beneficially modulates dimethyl benz (a)anthracene induced skin carcinogenesis and erhlich Ascites cell induced solid tumor in mice

The aim of this study was to assess the potential of chloroform extract of S. trilobatum (CST) on 7,12-dimethyl benz (a)anthracene (DMBA) induced skin carcinogenesis and Ehrlich ascites carcinoma cells (EAC) induced solid tumor in mice. CST was obtained by exhaustive extraction with chloroform. Skin carcinogenesis was induced in Swiss albino mice by applying DMBA, while solid tumor was induced by intramuscular injection of EAC cells. For preventing skin carcinogenesis, animals were treated with CST (5 mg/kg body weight/100 μl acetone) before and after DMBA application for 15 days. Solid tumor was treated with CST (400 mg/kg body weight) prophylatically and post inoculation. After the experimental period, several anti tumor parameters and antioxidant status of skin of treated and control animals were determined. Solid tumor progression was determined by measuring the tumor diameter for 36 days. CST was sub-fractionated with different solvents and each fraction was subjected to HPLC-MS. HPLC-MS analysis showed the presence of two components with possible anti-cancer activity viz. 3,5,7 trimethoxy flavone and vitexin per-O-acetyl. The biochemical results showed that CST treatment reduced the number of skin papillomas, tumor incidence as well as modulated the antioxidant status of the skin in a beneficial way. CST reduced the solid tumor volume induced by EAC significantly. In conclusion, CST with its biologically active components may be used as a part of cancer treatment.