Acanthus ilicifolius plant extract prevents DNA alterations in a transplantable Ehrlich ascites carcinoma-bearing murine model.

AIM: To investigate the chemopreventive efficacy of the Indian medicinal plant Acanthus ilicifolius L Acanthaceae in a transplantable Ehrlich ascites carcinoma (EAC)-bearing murine model. METHODS: Male Swiss albino mice were divided into four groups: Group A was the untreated normal control; Group B was the EAC control mice group that received serial, intraperitoneal (ip) inoculations of rapidly proliferating 2 x 10(5) viable EAC cells in 0.2 mL of sterile phosphate buffered saline; Group C was the plant extract-treated group that received the aqueous leaf extract (ALE) of the plant at a dose of 2.5 mg/kg body weight by single ip injections, once daily for 10, 20 and 30 consecutive days following tumour inoculation (ALE control); and Group D was the EAC + ALE-treatment group. The chemopreventive potential of the ALE was evaluated in a murine model by studying various biological parameters and genotoxic markers, such as tumour cell count, mean survival of the animals, haematological indices, hepatocellular histology, immunohistochemical expression of liver metallothionein (MT) protein, sister-chromatid exchanges (SCEs), and DNA alterations. RESULTS: Treatment of the EAC-bearing mice with the ALE significantly (P < 0.001) reduced viable tumour cell count by 68.34% (228.7 x 10(6) +/- 0.53) when compared to EAC control mice (72.4 x 10(6) +/- 0.49), and restored body and organ weights almost to the normal values. ALE administration also increased (P < 0.001) mean survival of the hosts from 35 +/- 3.46 d in EAC control mice to 83 +/- 2.69 d in EAC + ALE-treated mice. Haematological indices also showed marked improvement with administration of ALE in EAC-bearing animals. There was a significant increase in RBC count (P < 0.001), hemoglobin percent (P < 0.001), and haematocrit value (P < 0.001) from 4.3 +/- 0.12, 6.4 +/- 0.93, and 17.63 +/- 0.72 respectively in EAC control mice to 7.1 +/- 0.13, 12.1 +/- 0.77, and 30.23 +/- 0.57 respectively in EAC + ALE-treated group, along with concurrent decrement (P < 0.001) in WBC count from 18.8 +/- 0.54 in EAC control to 8.4 +/- 0.71 in EAC + ALE. Furthermore, treatment with ALE substantially improved hepatocellular architecture and no noticeable neoplastic lesions or foci of cellular alteration were observed. Daily administration of the ALE was found to limit liver MT expression, an important marker of cell proliferation with concomitant reduction in MT immunoreactivity (62.25 +/- 2.58 vs 86.24 +/- 5.69, P < 0.01). ALE was also potentially effective in reducing (P < 0.001) the frequency of SCEs from 14.94 +/- 2.14 in EAC control to 5.12 +/- 1.16 in EAC + ALE-treated group. Finally, in comparison to the EAC control, ALE was able to suppress in vivo DNA damage by abating the generations of 'tailed' DNA by 53.59% (98.65 +/- 2.31 vs 45.06 +/- 1.14, P < 0.001), and DNA single-strand breaks (SSBs) by 38.53% (3.14 +/- 0.31 vs 1.93 +/- 0.23, P < 0.01) in EAC-bearing murine liver. CONCLUSION: Our data indicate that, ALE is beneficial in restoring haematological and hepatic histological profiles and in lengthening the survival of the animals against the proliferation of ascites tumour in vivo. Finally, the chemopreventive efficacy of the ALE is manifested in limiting MT expression and in preventing DNA alterations in murine liver. The promising results of this study suggest further investigation into the chemopreventive mechanisms of the medicinal plant A. ilicifolius in vivo and in vitro.

Protective role of fish oil (Maxepa) on early events of rat mammary carcinogenesis by modulation of DNA-protein crosslinks, cell proliferation and p53 expression.

BACKGROUND: Fish oil is known to protect from many types of cancers of the colon, liver, breast, prostate and lung 123. The objective of the present study was to evaluate the role of fish oil [Maxepa, supplemented at a dose of 0.5 ml is equivalent to 90 mg eicosapentaenoic acid (EPA) and 60 mg docosahexaenoic acid (DHA)] on cell proliferation, expression of p53 tumor suppressor protein and DNA protein crosslinks (DPCs) in a defined model of chemical rat mammary carcinogenesis. Mammary carcinogenesis was initiated by a single, intravenous (i.v.) tail vein injection of 7,12 dimethylbenz(alpha)anthracene (DMBA) at a dose of 5 mg DMBA/2 ml corn oil/kg body weight in female Sprague-Dawley rats at 7 weeks of age. Fish oil supplementation was started daily, 2 weeks prior to DMBA injection and continued for 24 (31 weeks of animal age) weeks and 35 (42 weeks of animal age) weeks of post DMBA injection, for histopathological and immunohistochemical and for morphological studies, respectively. RESULTS: Our results indicate the chemopreventive effect of fish oil (Maxepa) on DMBA-induced rat mammary carcinogenesis. Administration of fish oil further showed a prominent reduction of cell proliferation (24.34%, P = 0.001); DPCs (25%, P < 0.001) and an increased expression of p53 protein (4.636 +/- 0.19, P < 0.001) in preneoplastic mammary tissue when compared to carcinogen control counterpart. Histopathological and morphological analyses were carried out as end-point biomarkers. CONCLUSION: Our study thus provides evidence for the anticarcinogenic effect of fish oil (Maxepa) in limiting mammary preneoplasia in Sprague-Dawley rats.

In vivo evaluation of antidiarrhoeal activity of Rhus semialata fruit extract in rats.

Rhus semialata Murr. (Anacardiaceae) is a deciduous tree of north eastern India. The fruit of this plant is traditionally used to control diarrhoea and dysentery. The Present study was undertaken to evaluate anti-diarrhoeal potency of methanol extract of fruits of R. semialata using Wister albino rats to substantiate folklore claims. The extract at graded doses (100, 200, 400 and 600 mg/kg body weight) was investigated for anti-diarrhoeal activity in term of reduction in the rate of defecation in castor oil induced diarrhoea. To understand the mechanism of its antidiarrhoeal activity, the gastrointestinal transit and PGE(2)-induced intestinal fluid accumulation (enteropooling) were further evaluated. At graded doses, the extract showed a remarkable anti-diarrhoeal activity evidenced by the reduction in the rate of defecation up to 80.70% of control diarrhoeal animals at the dose of 600 mg/kg body weight. Results are comparable to that of standard drug diphenoxylate (50 mg/kg body weight). Extract produced profound decrease in intestinal transit (8.02-47.05%) at selected doses comparable to that of single intraperitoneal injection of standard drug atropine sulphate at doses of 0.1 mg/kg body weight. It significantly inhibited PGE(2)-induced enteropooling (21.98-56.03%). The results indicated that the methanol extract of the fruits of R. semialata possesses significant anti-diarrhoeal effect and substantiated the use of this herbal remedy as a non-specific treatment for diarrhoea in folk medicine.

Vanadium, a versatile biochemical effector in chemical rat mammary carcinogenesis.

Recent studies indicate the role of the micronutrient vanadium in chemoprevention in many animal models, human cancer cell lines, and also in xenografted human carcinomas of the lung, breast, and gastrointestinal tract. The present studies were undertaken to ascertain the antineoplastic potential of vanadium in a defined model of mammary carcinogenesis. Female Sprague-Dawley rats, at 50 days of age, were treated with 7,12-dimethylbenz(alpha) anthracene (DMBA) (0.5 mg/100 g body weight) by a tail vein injection in oil emulsion. Vanadium (ammonium metavanadate) at a concentration of 0.5 ppm (4.27 micromol/l) was supplemented in drinking water and given ad libitum to the experimental group after the carcinogen treatment, and it continued until the termination of the study. In vivo studies of DNA chain breaks demonstrated that vanadium offered significant (61%, P<0.005) protection against generation of single-strand breaks when compared with the DMBA control group. Supplementation of vanadium normalizes the level of zinc, iron, and copper as revealed by proton-induced X-ray emission analysis to a substantial extent (P<0.01). In vitro study of chromosomal aberrations (CAs) revealed that vanadium triggered a protective effect (62.9%) on induction of CAs, which was maximum on structural aberrations followed by numerical and physiological types. Histopathological and morphological analyses were done as end-point biomarkers. We conclude herein that vanadium has the potential to reduce genomic instability in mammary carcinoma in rats.