Artemisinin as a Chinese medicine, selectively induces apoptosis in pancreatic tumor cell line / 中国结合医学杂志

<p><b>OBJECTIVE</b>To investigate the possible mechanism through which Artemisinin induced apoptosis in pancreatic cell line.</p><p><b>METHODS</b>Column chromatography, thin layer chromatography (TLC) and proton NMR spectroscopy were used to purify Artemisinin. The flowcytometry was employed to detect apoptosis and reactive oxygen species (ROS).</p><p><b>RESULTS</b>The results indicated that 50% inhibiting concentration (IC50 value) for pancreatic cell line (RIN) was 45 μmol/L of Artemisinin. Artemisinin had no cytotoxic effect on the growth of peripheral blood lymphocytes. The mechanism of apoptosis was evaluated by measuring intracellular ROS. It was shown that Artemisinin-induced apoptosis occurred independently of the binding of CD95L to CD95 receptor in the RIN cells. Moreover, Artemisinin, in a dose-dependent manner, could significantly increase the level of ROS.</p><p><b>CONCLUSION</b>Artemisinin can induce apoptosis in the RIN cells via the generation of ROS and triggering the intrinsic pathway of cell death.</p>

Sclareol reduces CD4+ CD25+ FoxP3+ t-reg cells in a breast cancer model in vivo

Sclareol is a phytochemical used in people's diet in Southeast Asia. To investigate the immunotherapeutic effectiveness of Sclareol against breast cancer by direct intraperitoneal injection. Sclareol was isolated and purified from Salvia sclarea. Effect of Sclareol on cell growth inhibition was evaluated by MTT assay. Intraperitoneally injected Sclareol effects on reducing the tumor volume and shifting the cytokine profile were investigated. We also assessed if intraperitoneally injected Sclareol could improve the outcome of cancer therapy through suppressing the regulatory T cells. The results confirmed a significant decrease in the tumor size. Furthermore, a significant decrease in the level of IL-4 and an increase in the level of IFN-gamma were noticed in the intraperitoneally injected Sclareol group [p<0.05]. It was also observed that the splenocytes of treated animals significantly increase in cell proliferation assay. Moreover, measurements of splenic T regulatory cell indicated that intraperitoneally injected Sclareol significantly decreased the number of splenic T regulatory cell. Our results suggest that Sclareol, by reducing T-reg cells frequency and also tumor size can enhance the effect of cancer therapy as an immunostimulant

Cytoxicity of root canal antiseptics used in dental practice on L929 fibroblasts: calcium hydroxide powder vs. 2% chlorhexidine solution

Chlorhexidine solution is one of the widely used mouth antiseptic liquid that prevents teeth tissue damage and also has application as a root canal antiseptic. In this study, cytotoxicity of 2% chlorhexidine solution is compared with another root canal antiseptic, calcium hydroxide powder. Cell cytotoxicity of both chemicals was assessed on cultured L929 fibroblastic cell line for 1, 12, 24, 48 and 72 hours using MTT assay [Methyl tetrazolium bromide assay]. Untreated L929 cells were used as a negative control group. MTT results were recorded by ELISA reader and analyzed using one-way ANOVA statistical tests. Cytotoxicity of studied chemicals showed significant difference in various dilutions and times [1, 12, 24, 48 and 72 h]. The highest cytotoxic effect of 2% chlorhexidine solution was observed in concentration of 0.016% for 72 h. Treatment of cells with 0.016% of 2% chlorhexidine liquid and calcium hydroxide powder for 72 hours showed 80% and 45% cytotoxicity, respectively. Cytotoxicity of calcium hydroxide is significantly less than 2% chlorhexidine liquid and then application of calcium hydroxide powder as root canal antiseptic is recommended

Long acting propranolol and HSP-70 rich tumor lysate reduce tumor growth and enhance immune response against fibrosarcoma in Balb/c mice

Noradrenaline [NA], the principal neurotransmitter released from sympathetic nerve terminals, influences T-cell maturation, not only directly in developing T cells, but also indirectly, by acting on the thymic nonlymphoid cells. In vitro and in vivo studies have demonstrated the anti-proliferative, anti-migratory, antiangiogenic and cytotoxic properties of propranolol, beta-AR blocker, against various cancers. To evaluate the effect of propranolol on efficacy of HSP-70 rich lysate vaccine in immunotherapy of fibrosarcoma. Mouse fibrosarcoma WEHI-164 cells were used to immunize tumor-bearing mice with or without propranolol and HSP-70. Splenocytes proliferation, cytotoxic activity of the splenocytes, naturally occurring CD4+ CD25[high] T-reg cells and IFN-gamma and IL-4 secretion as well as tumor size, were assessed to describe the anti-tumor immune response. A significant increase in the level of IFN- gamma in the mice vaccinated with WEHI-164 cells enriched with HSP-70 and co-treated with propranolol was observed compared to controls. However, HSP enrichment or propranolol treatment alone did not enhance the immune response as measured by the level of IFN-gamma. Likewise, a decrease in tumor growth in the test group [p<0.01] and a significant increase in CTL activity [p<0.05] was observed. HSP enriched vaccine shows anti-tumor activity, probably due to the modulation of immune responses

Tehranolide could shift the immune response towards Th1 and modulate the intra-tumor infiltrated T regulatory cells

Artemisia diffusa contains a new type of sesquiterpene lactone with an endoperoxide group [Tehranolide]. Due to the existing similarity between the structures of Tehranolide and Artemisinin, it was hypothesized that Tehranolide would have similar effects as Artemisinin. In this study, the immunotherapeutic effectiveness of Tehranolide was investigated by direct intra-tumoral injection. Tehranolide was purified from Artemisia diffusa, and its effect on the tumor volume was investigated. The splenocyte proliferation, shifting of cytokine profile, and the presence of naturally-occurring CD4+CD25+Foxp3+ Treg cells were assessed to describe the anti-tumor immune response. Analysis of immune response showed that, intra-tumoral injection of Tehranolide decreased the rate of tumor growth compared to control group. Furthermore, the proliferative response of mice treated with Tehranolide was enhanced. In comparison with the control group, production of both IL-4 and IFN-gamma was induced [p<0.05]. The results indicated a decrease in tumor CD4+CD25+Foxp3+ T lymphocytes in the Tehranolide-treated group compared to the control group. Treatment of tumors with Tehranolide attenuated CD4+CD25+Foxp3+ Treg cell-mediated immune suppression and elicited a persistent anti-tumor immunity against cancer