Anti-cancer effects of selective cannabinoid agonists in pancreatic and breast cancer cells

OBJECTIVE: Cancer ranks fi rst among the causes of morbidity and mortality all over the world, and it is expected to continue to be the main cause of death in the coming years. Therefore, new molecular targets and therapeutic strategies are urgently needed. In many cases, some reports show increased levels of endocannabinoids and their receptors in cancer, a condition often associated with tumour aggressiveness. Recent studies have suggested that cannabinoid-1/2 receptors contribute to tumour growth in a variety of cancers, including pancreatic, colon, prostate, and breast cancer. Understanding how cannabinoids can regulate key cellular processes involved in tumorigenesis, such as: cell proliferation and cell death, is crucial to improving existing and new therapeutic approaches for the cancer patients. The present study was aimed to characterize the in-vitro effect of L-759633 (a selective CB2 receptor agonist), ACPA (a selective CB1 receptor agonist) and ACEA (a selective CB1 receptor agonist) on the cell proliferation, clonogenicity, and apoptosis in pancreatic (PANC1) and breast (MDA-MB-231) cancer cells. METHODS: The viability and/or proliferation of cells were detected by MTS assay. A clonogenic survival assay was used to detect the ability of a single cell to grow into a colony. Apoptosis was determined with Annexin V staining (Annexin V-FITC/PI test) and by analyzing the expression of Bcl-2-associated X protein (Bax) and B-cell lymphoma 2 (Bcl-2). RESULTS: We found that selective CB1/2 agonists suppressed cell proliferation, clonogenicity and induced proapoptotic function in human PANC1 pancreatic and MDA-MB-231 breast cancer cells. Based on our fi ndings, these agonists led to the inhibition of both cell viability and clonogenic growth in a dose dependent manner. CB1/2 agonists were observed to induce intrinsic apoptotic pathway by upregulating Bax, while downregulating Bcl-2 expression levels. CONCLUSION: Our data suggests that CB1/2 agonists have the therapeutic potential through the inhibition of survival of human PANC1 pancreatic and MDA-MB-231 breast cancer cells and also might be linked with further cellular mechanisms for the prevention (Fig. 5, Ref. 49). Text in PDF www.elis.s

The influence of quercetin on recognition memory and brain oxidative damage in a ketamine model of schizophrenia

OBJECTIVE: The aims of this study were to investigate the protective effect of quercetin on changes in recognition memory as assessed by the novel object recognition (NOR) test, as well as on changes in the oxidative stress levels in the hippocampus and prefrontal cortex, produced in a model of memory impairment in schizophrenia induced by administration of a subanesthetic dose of ketamine. METHODS: A total of 40 Balb-C mice were randomly divided into five groups (Corn oil + Saline, Quercetin 50 + Saline, Corn oil + Ketamine, Quercetin 25 + Ketamine, Quercetin 50 + Ketamine). Corn oil and Quercetin (25 or 50 mg/kg/day) was given by orogastric gavage once daily for 21 days. Corn oil was chosen as the vehicle and administered at the same volume as quercetin. Ketamine was injected at a dose of 25 mg/kg intraperitoneally (i.p.) for a period of 7 days starting from the 15th day. Behavioural responses were evaluated with the NOR test. The activity levels of antioxidant enzymes and levels of malondialdehyde (MDA) were assayed in the prefrontal cortex and hippocampus. RESULTS: The time of exploration of the novel object was longer than TF (time to explore the familiar object) in the Corn oil + Saline and Quercetin 50 + Saline groups in NOR Test-1 (p < .05). The discrimination ratios of the Quercetin 50 + Ketamine and Corn oil + Ketamine groups were significantly lower than that of the Quercetin 50 + Saline group (p < .05). The discrimination ratios of the Quercetin 50 + Ketamine and Corn oil + Saline groups were significantly lower than that of the Quercetin 50 + Saline group (p < .05). The time of exploration of the novel object was longer than TF in the Corn oil + Saline and Quercetin 50 + Ketamine groups in NOR Test-2 (p < .05). The discrimination ratios of the Corn oil + Ketamine and Quercetin 25 + Ketamine groups were significantly lower than those of the Quercetin 50 + Ketamine group (p < .05). Quercetin at 50 mg/kg reduced the MDA levels and elevated the SOD and GPx activity compared to the Corn oil + Ketamine group. CONCLUSION: These results show that quercetin has the potential to improve cognitive deficits in mice and that quercetin may be useful for treating the symptoms of schizophrenia, partially due to its ability to scavenge free radicals and its high antioxidant capacity

Strontium chloride hexahydrate as a candidate molecule for long-term treatment of allergic rhinitis

Background & objectives: Neurogenic inflammation plays a role in the pathophysiology of allergic rhinitis (AR). Strontium salts are highly effective in reducing the sensory irritation. This study was aimed to investigate the efficacy of strontium chloride (SC) on AR symptoms based on the duration of SC use before the symptoms begin. Methods: Wistar albino rats (n=18) were randomly divided into three groups: Group 1, received 1μg mometasone furoate (MF); Group 2, three per cent SC; and Group 3 received five per cent SC (2 μl/site). Drugs were administered to the each nasal cavity for three weeks every morning. On the days 7, 14 and 21, histamine dihydrochloride (HD) 5 μmol (2 μl/site) was administered and the frequencies of nasal rubbing and sneezing were counted for 15 min. Results: After 7, 14 and 21 day medication period, the groups were compared in terms of the frequency of sneezing and nasal rubbing following HD. There was a significant difference among the groups in terms of the frequency of sneezing on the day 7 (P< 0.05). Intragroup comparisons for the nasal rubbing showed significance (P< 0.05). In Group 3, there was a decrease in the number of nasal rubbings on the day 14 and 21; however, the difference was not significant. Interpretation & conclusions: Our results showed that three and five per cent SC were less effective than MF for sneezing during the first week, but the efficiency was equal to that of MF after the first 14 days. Long-term use of SC was as effective as MF on nasal rubbing. SC can be as effective as MF on both sneezing and nasal rubbing on regular use over three weeks

The effect of octreotide, an analog of somatostatin, on bleomycin-induced interstitial pulmonary fibrosis in rats

In this study, octreotide (OCT), a synthetic sonnatostatin analog, was tested for its beneficial effects in the prevention of interstitial pulmonary fibrosis (IPF) induced by bleomycin (BLM) in rats by histological examination and by evaluating tissue OH-proline levels. Thirty male Wistar rats were divided randomly into three groups: group I: intratracheal (i.t.) BLM (7.5 mg/kg, single dose) + saline solution [0.9% NaCl, subcutaneously (s.c.), once-daily for 7 days]; group II: i.t. BLM (7.5 mg/kg, single dose) + OCT acetate (82.5 mu g/kg, s.c., once-daily for 7 days); and the control group. At the end of the 7 days, lung tissues were excised and examined by histopathological methods. Levels of tissue hydroxyproline (OH-proline) were determined. BLM administration resulted in prominent histopathologic findings, such as diffuse alveolar damage and interstitial pulmonary fibrosis, as well as a significant increase in OH-proline level, as compared to controls. OCT application explicitly attenuated the histopathologic changes to a significant extent. OCT decreased paranchymal fibrosis and structural deformities in BLM-induced lung fibrosis. These results suggest that OCT administration to rats with BLM-induced IPF has a protective effect. Further studies are necessary to reveal the molecular mechanism(s) of OCT-induced protective effect

Effect of black mulberry (Morus nigra) extract treatment on cognitive impairment and oxidative stress status of d-galactose-induced aging mice

Context: Morus nigra L. (Moraceae) has various uses in traditional medicine. However, the effect of M. nigra on cognitive impairment has not been investigated yet