Anticancer and antimutagenic properties of Acacia nilotica (Linn.) on 7,12-dimethylbenz(a)anthracene-induced skin papillomagenesis in Swiss albino mice.

We report the chemopreventive activity of Acacia nilotica (Linn.) gum, flower and leaf aqueous extracts, on 7,12-dimethylbenz(a)anthracene (DMBA) induced skin papillomagenesis in male Swiss albino mice. Animals were divided into following groups: Group I (Controls) given DMBA and croton oil, with no extract ; Group II (treatment) animals treated with Acacia nilotica gum (Group II-a) (800 mg/kg body weight), flowers (Group II-b) (800 mg/kg body weight), or leaves (Group II-c) (800 mg/kg body weight) during the peri- and post initiation periods of DMBA and croton oil application. A significant reduction in the values of tumor burden, tumor incidence and cumulative number of papillomas was observed in mice treated by oral gavage with the Acacia nilotica gum, flower and leaf extracts as compared with the control group. The latency period in treatment Group-II (b) and Group-II (c) was significantly increased as compared with the control group. A significant reduction in the frequency of micronuclei was also observed in mice treated by oral gavage with the aqueous extracts, along with significant decrease in total chromosomal aberrations in the form of chromatid breaks, chromosome breaks, centric rings, dicentrics, acentric fragments and exchange. Treatment with Acacia nilotica flower (Group II-B) and leaf (Group II-C) aqueous extracts by oral gavage for 15 days resulted in a highly significant decrease in the lipid peroxidation (LPO) level in the liver, but this was less evident with the gum (Group II-A) . Conversely, reduced glutathione (GSH) content was observed to be significantly elevated as compared with the control group with leaves (Group II-C) and flowers (Group II-B). The chemopreventive and antimutagenic activity of the leaf extract of Acacia nilotica was most significant followed by the flower extract and then by gum.

Chemopreventive potential of Tribulus terrestris against 7,12- dimethylbenz (a) anthracene induced skin papillomagenesis in mice.

In the present investigation, the chemopreventive potential of aqueous extracts of the root and fruit of Tribulus terrestris (an Ayurvedic medicinal plant) on 7, 12 - dimethylbenz (a) anthracene (DMBA) induced papillomagenesis in male Swiss albino mice was studied. A significant reduction in tumor incidence, tumor burden and cumulative number of papillomas was observed, along with a significant increase in average latent period in mice treated orally with Tribulus terrestris suspension continuously at pre, peri and post-initiation stages of papillomagenesis as compared to the control group treated with DMBA and croton oil alone. Treatment with Tribulus terrestris suspension by oral gavage for 7 days resulted in a significant increase in the reduced glutathione content in the liver (P< 0.001 for both root and fruit extracts). Conversely, lipid peroxidation levels were significantly decreased (P< 0.001).

Modulatory influence of Rosemarinus officinalis on DMBA-induced mouse skin tumorigenesis.

The present investigation was undertaken to explore the anti-tumor promoting activity of Rosemarinus officinalis on two-stage skin carcinogenesis, induced by a single topical application of 7, 12-dimethylbenz(a)anthracene and promoted by treatment of croton oil for 15 weeks in Swiss albino mice. Oral administration of Rosemary leaf extract at a dose of 1,000 mg/ kg b. wt. / day at pre, peri and post-initiational phases, was found to be effective in decreasing the tumor incidence (50, 41.7, 58.3%, respectively) in comparison to the control (100%). Furthermore, the cumulative number of papillomas, tumor yield and tumor burden were also found to be reduced in R. officinalis-treated animals. This was associated with significant alteration in liver lipid peroxidation and glutathione (GSH) levels.

Chemopreventive action of emblica officinalis on skin carcinogenesis in mice.

Chemoprevention with food phytochemicals is currently regarded as one of the most important strategies for cancer control. Emblica officinalis (Family: Euphorbiaceae) indigenous to India, is valued for its unique tannins and flavanoids, which contain very powerful antioxidant properties. The inhibition of tumor incidences by fruit extract of this plant has been evaluated on two-stage process of skin carcinogenesis in Swiss albino mice, induced by a single application of 7, 12-dimethyabenz(a)anthrecene (100 microg / 100 microl acetone), and two weeks later, promoted by repeated application of croton oil (1% in acetone/thrice a week) till the end of the experiment (16 weeks). The tumor incidence, tumor yield, tumor burdon and cumulative number of papillomas were found to be higher in the control (without EO treatment) as compared to experimental animals (EO treated). The differences in the values of the results of experimental groups were statistically analysed and found to be significant in comparison to the control group (p< 0.05). The present study demonstrates the chemopreventive potential of Emblica officinalis fruit extract on DMBA induced skin tumorigenesis in Swiss albino mice.

Anti-tumour promoting activity of diphenylmethyl selenocyanate against two-stage mouse skin carcinogenesis.

Epidemiological, clinical and experimental evidence collectively suggests that Se in different inorganic and organic forms provides a potential cancer chemopreventive agent, active against several types of cancer. It can exert preventive activity in all the three stages of cancer: initiation, promotion and progression. Literature reports revealed that organoselenocyanates have more potential as chemopreventive agents than inorganic forms due to their lower toxicity. In our previous report we showed chemopreventive efficacy of diphenylmethyl selenocyanate during the initiation and pre- plus post-initiation phases of skin and colon carcinogenesis process. The present study was undertaken to explore the anti-tumour promoting activity of diphenylmethyl selenocyanate in a 7,12-dimethylbenz (a) anthracene (DMBA)-croton oil two-stage skin carcinogenesis model. The results obtained showed significant (p<0.01) reduction of the incidence and number of skin papillomas, precancerous skin lesions, along with significant (p<0.01) elevation of phase II detoxifying enzymes (GST, Catalase and SOD) and inhibition of lipid peroxidation in liver and skin. Thus, the present data strongly suggest that diphenylmethyl selenocyanate also has the potential to act as anti-tumour promoter agent in a two-stage skin carcinogenesis mouse model, pointing to possible general efficacy.

Modulation of antioxidant potential in liver of mice by kernel oil of cashew nut (Anacardium occidentale) and its lack of tumour promoting ability in DMBA induced skin papillomagenesis.

Cashew nut shell oil has been reported to possess tumour promoting property. Therefore an attempt has been made to study the modulatory effect of cashew nut (Anlacardium occidentale) kernel oil on antioxidant potential in liver of Swiss albino mice and also to see whether it has tumour promoting ability like the shell oil. The animals were treated orally with two doses (50 and 100 microl/animal/day) of kernel oil of cashew nut for 10 days. The kernel oil was found to enhance the specific activities of SOD, catalase, GST, methylglyoxalase I and levels of GSH. These results suggested that cashew nut kernel oil had an ability to increase the antioxidant status of animals. The decreased level of lipid peroxidation supported this possibility. The tumour promoting property of the kernel oil was also examined and found that cashew nut kernel oil did not exhibit any solitary carcinogenic activity.

Chemopreventive action of Phyllanthus urinaria Linn on DMBA-induced skin carcinogenesis in mice.

The inhibition of tumor incidence by hydro-alcoholic extract of the whole plant of P. urinaria was evaluated in 6-7 weeks old female albino mice on two-stage process of skin carcinogenesis induced by a single application of 7,12-dimethylbenz(a)anthracene (50 microg/50 microl of acetone), and 2 weeks later, promoted by repeated application of croton oil (1% in acetone/three times a week) till the end of the experiment (15 weeks). Topical application of the extract at a dose of 5 mg/kg body weight/day for 15 weeks at the peri-initiational stage (i.e., 7 days before and 7 days after DMBA application), promotional stage (i.e., from the time of croton oil application) and both peri and post-initiational stages (i.e., 7 days prior to DMBA application and continued till the end of the experiment) on the shaven backs of the mice recorded a significant reduction in tumor incidence to 50, 33.3 and 16.7% respectively in comparison to the control (i.e., the mice treated with DMBA and croton oil only) where tumor incidence was found to be 81.8%. The average number of papillomas per mouse was also significantly reduced. The results suggest a possible chemopreventive property of P. urinaria against DMBA-induced skin papillomagenesis in mice.

Chemopreventive action of Boerhaavia diffusa on DMBA-induced skin carcinogenesis in mice.

Boerhaavia diffusa, Linn (Fam: Nyctagenaceae), is widely used for the treatment of Jaundice in various parts of India. In the present study, cancer chemopreventive property of B. diffusa was evaluated on 7,12-dimethyl benz(a)anthracene (DMBA) induced skin papillomagenesis in male Swiss albino mice (6-7 weeks old). A single topical application of 7,12-dimethyl benz(a)anthracene (50 microg/50 microl of acetone), followed 2 weeks later by repeated application of croton oil (1% in acetone three times a week) and continued till the end of the experiment exhibited 100% tumor incidence. In contrast, mice treated topically on the shaven backs with the Boerhaavia diffusa extract at either the peri-initiational phase (i.e. 7 days before and 7 days after the application of DMBA; Group II), post initiational phase (i.e. from the day of start of croton oil treatment and continued till the end of the experiment; Group III) or continuously at the peri- and post-initiational stages (i.e. 7 days prior to DMBA application and continued till the end of the experiment; Group IV), a significant reduction in the values of tumor incidence (Group II - 65%; Group III - 30%; Group IV - 25%), average number of tumors per tumor bearing mouse (Group II - 2.8; Group III - 0.75; Group IV - 0.35) and papillomas per papilloma bearing mouse (Group II - 3.1; Group III - 2.5; Group IV - 1.2) were observed.

Chemomodulatory effect of Moringa oleifera, Lam, on hepatic carcinogen metabolising enzymes, antioxidant parameters and skin papillomagenesis in mice.

The modulatory effects of a hydro-alcoholic extract of drumsticks of Moringa oliefera Lam at doses of 125 mg/kg bodyweight and 250 mg/ kg body weight for 7 and 14 days, respectively, were investigated with reference to drug metabolising Phase I (Cytochrome b(5) and Cytochrome p(450) ) and Phase II (Glutathione-S- transferase) enzymes, anti-oxidant enzymes, glutathione content and lipid peroxidation in the liver of 6-8 week old female Swiss albino mice. Further, the chemopreventive efficacy of the extract was evaluated in a two stage model of 7,12 - dimethylbenz(a)anthracene induced skin papillomagenesis. Significant increase (p<0.05 to p<0.01) in the activities of hepatic cytochrome b(5), cytochrome p(450), catalase, glutathione peroxidase ( GPx ), glutathione reductase (GR), acid soluble sulfhydryl content (-SH ) and a significant decrease ( p<0.01 ) in the hepatic MDA level were observed at both dose levels of treatment when compared with the control values. Glutathione-S- transferase ( GST )activity was found to be significantly increased (p<0.01 ) only at the higher dose level. Butylated hydroxyanisol (BHA ) fed at a dose of 0.75% in the diet for 7 and 14 days (positive control ) caused a significant increase (p<0.05 to p<0.01) in the levels of hepatic phase I and phase II enzymes, anti- oxidant enzymes, glutathione content and a decrease in lipid peroxidation. The skin papillomagenesis studies demonstrated a significant decrease (p<0.05 ) in the percentage of mice with papillomas, average number of papillomas per mouse and papillomas per papilloma bearing mouse when the animals received a topical application of the extract at a dose of 5mg/ kg body weight in the peri-initiation phase 7 days before and 7 days after DMBA application, Group II ), promotional phase (from the day of croton oil application and continued till the end of the experiment, Group III ) and both peri and post initiation stages (from 7 days prior to DMBA application and continued till the end of the experiment, Group IV) compared to the control group (Group I ). The percentage inhibition of tumor multiplicity has been recorded to be 27, 72, and 81 in Groups II, III, and IV, respectively. These findings are suggestive of a possible chemopreventive potential of Moringa oliefera drumstick extract against chemical carcinogenesis.

Inhibition of tumour promotion in mice by eugenol.

Number of tumours (papillomas) produced by the application of 7,12-dimethyl benz (a) anthracene as initiator and croton oil promoter in mice were considerably inhibited (84%) by the prior application of eugenol. Moreover, there was considerable decrease in the number of tumour bearing animals and their onset. Eugenol inhibited superoxide formation and lipid peroxidation and the radical scavenging activity may be responsible for its chemopreventive action.

Chemopreventive action of Liv. 52 on DMBA-induced papillomagenesis in skin of mice.

DMBA (195 nmol/50 microliters of acetone/animal) was applied topically over the dorsal skin of the mice and tumors were promoted by repeated applications of croton oil (1% in acetone, three times per week) after two weeks of DMBA application. Skin papillomas appeared in 100% animals in control as well as in groups treated orally with Liv. 52 at post-initiational stages and continuously at peri-initiational and post-initiational stages of papillomagenesis. When Liv. 52 was given orally at the peri-initiational stage of papillomagenesis, the percentage of mice bearing tumors was 75% and the tumor mean per mouse was reduced to 4.0 +/- 1.63 as compared to 7.5 +/- 3.54 in the control group after 15 weeks of observation. The tumor mean per mouse was observed to be 4.75 +/- 0.55 and 2.5 +/- 0.57 in the groups treated orally with Liv. 52 at the post-initiational stages and continuously at peri-initiational and post-initiational stages of papillomagenesis respectively. Similarly, the cumulative number of papillomas after 15 weeks was 30 in the control group, which was reduced to 10 in the animals treated with Liv. 52 continuously at peri-initiational and post-initiational stages. The cumulative number of papillomas was also reduced to 16 and 19 in animals treated with Liv. 52 at peri-initiational and post-initiational stages, respectively.

Correlation between tissue growth kinetics and modulation of mouse skin tumorigenesis by phorbol esters.

Previous studies on the influence of phorbol esters on mouse skin tumorigenesis have shown that 12-O-tetradecanoylphorbol-13-acetate (TPA) enhances development of malignant epithelial and mesenchymal skin tumors by a completely carcinogenic dose of 3-methylcholanthrene (MCA), while its congener phorbol-12, 13-diacetate (PDA) exerts an inhibitory effect. Differential effects of these two agents were analysed by histology, morphometry and cell kinetic techniques including autoradiography and estimation of labelled precursor incorporation into DNA by liquid scintillation counting. Epidermal hyperplasia induced on exposure of S/RV Cri mouse skin to a single or multiple TPA application after MCA injection was associated with a significant increase in the thickness of nucleated cell layers, stratum granulosum, number of suprabasal cells and dark basal cells. Enhancing effect of TPA on MCA-induced neoplastic development correlated well with an increase in mitotic activity, number of cells in S-phase and increased rate of DNA synthesis in the epidermis, dermis and subcutis as also mast cell number. In contrast, treatment of MCA-injected preneoplastic mouse skin with PDA resulted in epidermal hypoplasia and cellular damage evident as cytoplasmic vacuolation and nuclear pyknosis. Multiple PDA exposure also reduced the thickness, mitotic index and number of cells in S-phase in epidermis, dermis and subcutis. Thus, cellular toxicity and inability to recruit cells in DNA-synthetic phase may account for inhibition of progression of preneoplastic epithelial and mesenchymal cells into overt tumors by PDA.

Periodic histopathological and ultrastructural changes of excess vitamin A on oral carcinogenesis.

In this study initially a precancerous condition, leukoplakia, was develop at 6 weeks treatment of DMBA whereas in the animals treated both DMBA + Vit. A, leukoplakia was seen at 10 weeks followed by papilloma or nodules at 12 weeks. Tumours induced by DMBA were more in number than DMBA + Vit. A treated tumours. The histological and ultrastructural changes were enhanced and prominent in DMBA treated animals at 12 weeks, where as these changes were considerably less in animals treated with DMBA + vit. A at 12 weeks.