We evaluated the ability of cannabidiol (CBD) to impair the migration of tumor cells stimulated by conditioned medium. CBD caused concentration-dependent inhibition of the migration of U87 glioma cells, quantified in a Boyden chamber. Since these cells express both cannabinoid CB1 and CB2 receptors in the membrane, we also evaluated their engagement in the antimigratory effect of CBD. The inhibition of cell was not antagonized either by the selective cannabinoid receptor antagonists SR141716 (CB1) and SR144528 (CB2) or by pretreatment with pertussis toxin, indicating no involvement of classical cannabinoid receptors and/or receptors coupled to Gi/o proteins. These results reinforce the evidence of antitumoral properties of CBD, demonstrating its ability to limit tumor invasion, although the mechanism of its pharmacological effects remains to be clarified.

INTRODUCTION: Homeopathy is a popular form of complementary and alternative medicine and is used to treat for certain liver ailments. AIM: To analyze the efficacy of homeopathic Chelidonium majus (Chel) 30C and 200C in amelioration of experimentally induced hepato-toxicity in rats. METHODS: Rats were randomized into six sub-groups: negative control; negative control+EtOH; positive control; positive control+EtOH group; Chel 30; Chel 200. Rats were sacrificed at day 30, 60, 90 and 120; various toxicity biomarkers and pathological parameters were evaluated. Gelatin zymography for determination of metalloproteinases activity and Western blot of p53 and Bcl-2 proteins were also employed. All analyses were observer blind. RESULTS: Chronic feeding of p-dimethyl amino azo benzene (p-DAB) and phenobarbital (PB) elevated the levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma glutamyl transferase (GGT), lactate dehydrogenase (LDH), triglyceride, cholesterol, creatinine and bilirubin and lowered the levels of glutathione (GSH), glucose-6-phosphate dehydrogenase (G-6-PD), catalase and HDL-cholesterol. There were statistically significant modulations of these parameters in the treated animals, compared to positive controls. In both treated groups, there was downregulation of metalloproteinases, p53 and Bcl-2 proteins compared to over-expression in the positive control groups. CONCLUSION: Both the potencies of Chel exhibited anti-tumor and anti-oxidative stress potential against artificially induced hepatic tumors and hepato-toxicity in rats. More studies are warranted.

We have already reported that the D-Fraction, a beta-glucan extracted from the fruiting body of the maitake mushroom (Grifola frondosa), activates cellular immunity and expresses anti-tumor effects. In this study we investigated the anti-tumor functions of D-Fraction in relation to its control of the balance between T lymphocyte subsets Th-1 and Th-2. D-Fraction decreased the activation of B cells and potentiated the activation of helper T cells, resulting in enhanced cellular immunity. It also induced the production of interferon (IFN)-gamma, interleukin (IL)-12 p70, and IL-18 by whole spleen cells and lymph node cells, but suppressed that of IL-4. These results suggest that D-Fraction establishes Th-1 dominance which induces cellular immunity in the population that was Th-2 dominant due to carcinoma.

Photoactivation of hypericin is known to generate singlet oxygen and superoxide anion radicals. Reactive oxygen species (ROS) produced by photodynamic therapy (PDT) has the capacity to induce oxidative damage and tumor destruction. We have previously shown that hypericin-PDT induces tumor shrinkage and regression in the human nasopharyngeal cancer (NPC)/HK1 murine tumor model. In this extended study, we show by electron microscopy that subcutaneously implanted HK1 NPC cells from Balb/c nude mice perished by cell necrosis with hypericin-PDT treatment. There was evidence of cytoplasmic swelling accompanied by loss of cell membrane integrity and autophagic vacuolization of cytoplasm but no nuclear changes. There was also no significant difference in the apoptotic index of control and PDT-treated tumors, when analyzed by in situ end labeling of DNA strand breakage to detect apoptosis. This further supports the observation that cell death in PDT-treated NPC/HK1 tumors was by necrosis. Lipid peroxidative stress analyzed by the malonaldehyde assay was significantly elevated in PDT-treated cells. However, PDT had no effect on the activity of superoxide dismutase, an intracellular antioxidant enzyme. The findings show that hypericin-PDT of nasopharyngeal tumors in vivo induces tumor necrosis with accompanying lipid peroxidation.

Loss of parietal cells initiates the development of spasmolytic polypeptide-expressing metaplasia (SPEM), a precancerous lesion in stomach. CD44 variant (CD44v) which enhances the ability to defend against reactive oxygen species (ROS) in epithelial cells is expressed de novo in SPEM of K19-Wnt1/C2mE mice, a transgenic model of gastric tumorigenesis, and is required for the efficient development of SPEM and gastric tumor in these animals. The role of ROS and its downstream signaling in CD44-dependent gastric tumorigenesis has remained unknown, however. With the use of the K19-Wnt1/C2mE mouse we now show that parietal cells in the inflamed stomach are highly sensitive to oxidative stress and manifest activation of p38MAPK signaling by ROS. Oral treatment with the antioxidant ascorbic acid or genetic ablation of the Ink4a/Arf locus, a major downstream target of ROS-p38MAPK signaling, inhibited parietal cell loss and the subsequent gastric tumorigenesis. Our results indicate that signaling activated by oxidative stress in parietal cells plays a key role in CD44-dependent gastric tumorigenesis.

The influence of adult stem cells on tumor growth is paradoxical. On one hand, angiogenic factors secreted by stem cells are known to be essential for tumor vascularization. On the other hand, stem cell-derived factors can reportedly induce tumor differentiation or direct death of tumor cells. Both the placenta and umbilical cord are rich sources of stem cells with immune modulatory and tissue-healing properties; however, the effects of placental components on cancer cells have not been fully defined. Here we demonstrate that extracts of placental lysates reduce the malignancy of a variety of human tumor cell lines in a species-unrestricted manner. Using a standard model of leukemia cell differentiation, we demonstrated that addition of placental extracts to tumor cells, or co-culture of tumor cells with the CD34(+) cells from umbilical cord blood, induced tumor cell differentiation. Inhibition of tumor growth and metastasis in vivo was also observed following administration of placental extracts. These data support the concept of non-toxic biological therapy of cancer using stem cell derivatives, possibly through the induction of tumor cell differentiation.