Chronic lymphocytic leukemia (CLL) remains an incurable disease that requires innovative new approaches to improve therapeutic outcome. Many Ferula species, including F. asa-foetida, synthesize terpenyloxy coumarins. One of these coumarins is UMBELLIPRENIN, which has been implicated with induction of apoptosis in some cancer cell lines.In this study induction of apoptosis by UMBELLIPRENIN on Jurkat T-CLL and Raji B-CLL cell lines was studied. In this regard, cells were incubated with various concentrations of UMBELLIPRENINin-vitro for different times and assayed for apoptosis with annexin V–FITC/PI double staining flowcytometry method. Results showed that UMBELLIPRENIN induced apoptosis in leukemic cells in a dose- and time-dependent manner and that CLL cells were more susceptible to UMBELLIPRENIN induced cell death than normal peripheral blood mononuclear cell (PBMCs).Moreover, we study the induction of apoptosis in Jurkat cells by UMBELLIPRENIN in the presence of interleukin 4 (IL-4) as an agent that causes resistance to apoptosis in CLL cells, was also student. We showed that IL-4 can not reduce apoptotic effect of UMBELLIPRENIN.The preferential toxicity of UMBELLIPRENIN for CLL cells, supports the hypothesis that oral administration of UMBELLIPRENIN in the form of foods or folk medicines containing this coumarin, might enhance protection against the development of CLL in man with little side effects. In conclusion, UMBELLIPRENIN may be an effective therapeutic agent in the treatment of CLL, and thus clinical studies with UMBELLIPRENIN may be appropriate.

Background: Colon carcinoma growth depends on many factors such as, different organisms, and immune cells, which induce and produce inflammatory cytokines. UMBELLIPRENIN is a naturally prenylated coumarin with anti-inflammatory activities. Its ability to induce cancer cell death has shown variation on different cancer cell lines.Objectives: 7-Prenyloxycoumarins, including UMBELLIPRENIN have been widely investigated because of their pharmacological activities. This paper shows the effect of UMBELLIPRENIN on colon cancer cell lines.Material and Methods: In the present study, invasive SW48 and noninvasive SW1116 were treated with UMBELLIPRENIN (6.25, 12.5, 25, 50, 100, and 200 mM), and the cytotoxicity was determined using a methyl thiazolelydiphenyl-tetrazolium bromide (MTT) assay.Results: UMBELLIPRENIN had significant cytotoxic activity against SW48 cells at all study concentrations (except for 6.25 mM), with IC50 values of 117, 77, and 69 mM after 24, 48, and 72 h, respectively. However, it was cytotoxic against SW1116 only at higher concentrations of 100 and 200 mM (34% and 64% cell death). At lower concentrations, UMBELLIPRENIN showed a significant proliferative effect on this noninvasive cancer cell line. Our data were validated by eye and microscopic images.Conclusions: We found a moderate cytotoxic activity of UMBELLIPRENIN against invasive SW48 cells, and both cytotoxic and proliferative effects on noninvasive SW1116 cells. Therefore, using UMBELLIPRENIN as an anti-inflammatory or cytotoxic compound for patients with colon cancer should be used with care.

UMBELLIPRENIN is a sesquiterpene coumarin with vitro anti-carcinogenic activities. The aim of this study was to investigate the antitumor effects of UMBELLIPRENIN in animal models of colorectal cancer. The cytotoxic effects of UMBELLIPRENIN were explored on CT26 and L929by MTT assay. In this study, colorectal tumors developed in mice by intradermal injection ofCT26 cell line. Tumor size, serum levels of IFN- g and IL-4 by ELISA, and Ki-67, MMP2, MMP9, VEGF and E-cadherin markers by IHC method were evaluated. The results showed that UMBELLIPRENIN inhibited the cancer cells in a concentration-dependent manner. IC50 Evaluation showed that L929 cells were more resistant to UMBELLIPRENIN than CT26 cells. UMBELLIPRENIN treatment in both tumor-bearing mice and control normal mice showed significantly increased IFN-g and decreased IL-4 (P<0.05). The pathologic findings had shown that the E-cadherin marker in the UMBELLIPRENIN treated cancerous mice were significantly higher compared to the control group (P<0.05) while the expression of Ki-67 marker was reduced significantly (P<0.05). Markers involved in angiogenesis including VEGF, MMP2, and MMP-9 in the cancerous mice group treated with UMBELLIPRENIN showed a significant decrease compared to the control group (P<0.05). Metastasis to lung and liver was reduced in UMBELLIPRENIN treated group. Our results showed that UMBELLIPRENIN inhibited CT26 tumor cells in-vitro. The in-vivo reduction of tumor size, angiogenesis, and proliferation markers and the absence of metastasis represents the antitumor effects of UMBELLIPRENIN on colorectal cancer. The results showed that UMBELLIPRENIN can be considered as a good candidate for the treatment of colorectal cancer.

Objective(s): UMBELLIPRENIN is a prenyloxy-coumarin with pharmacologically polyvalent activity. Several studies have shown Several studies have been shown its anti-inflammatory, anti-tumor, antioxidant, and antigenotoxic activities. However, the exact mechanism of action of this compound on the immune response has not yet been shown. Here, we investigated UMBELLIPRENIN effects on the predominance of Th1 and Th2 responses in normal C57/BL6 mice.Materials and Methods: UMBELLIPRENIN (2.5 mg/200 ml IP) were administered to six C57/BL6 mice every other day for 8 days. Paraffin and PBS-injected mice were enrolled as solvent and control groups, respectively (n=6 mice/group). IL-10, IFN-g, and IL-4 levels were determined in sera and also in splenocytes culture supernatants in the presence of Con A (3 mg/ml) after 72 hr. H& E staining of paraffin embedded blocks was performed for lung and liver tissues of mice.Results: UMBELLIPRENIN could significantly increase the secretion of IFN-γ and IL-4 in sera and IL-10 in splenocytes cultures. Comparison of IFN-g /IL-4 in the sera and splenocytes culture supernatants showed lower ratios in UMBELLIPRENIN treated mice than in solvent and untreated groups.Conclusion: The in vivo study showed that UMBELLIPRENIN could induce anti-inflammatory responses via the predominance of Th2 cells and some regulatory responses in C57/BL6 mice.

Chronic lymphocytic leukaemia (CLL) is the most common B-cell malignancy in the western world and exists as subtypes with very different clinical courses. Myeloid cell leukemia 1 (Mcl-1) is one member of Bcl-2 family proteins that has been shown to be expressed in various tissues and malignant cells, including CLL, where its expression is significantly associated with a failure to achieve complete remission following cytotoxic therapy.Induction of apoptosis by prenylated coumarin, UMBELLIPRENIN, in Jurkat cells was previously shown. We examined whether UMBELLIPRENIN can down-regulate Mcl-1 gene and protein in Jurkat cells. In this regard cells were incubated by UMBELLIPRENIN, and then down- regulation of Mcl-1 gene was studied by Real Time PCR method. Moreover, down-regulation of Mcl-1 protein was studied by western blot analysis.We showed that, expression of Mcl-1 mRNA was increased from 1 hour to 3 hours incubation٫ but this increase has a scale down pattern. Moreover UMBELLIPRENIN could inhibit Mcl-1 protein. In conclusion UMBELLIPRENIN treatment modulates Mcl-1 expression at both the transcriptional and posttranslational levels.

Background and objective: UMBELLIPRENIN, the natural prenylated coumarin distributed in the plants of apiaceae family, has shown various biological activities, especially as a cancer chemo preventive agent. In the present study, UMBELLIPRENIN, was examined for in vitro antioxidant activity, in vitro inhibitory activity against lipoxygenase, and in vivo anti-inflammatory activity.Methods: The applied tests were interaction with 1,1-diphenyl-2-picryl-hydrazyl (DPPH) stable free radical, inhibition of lipid per oxidation, inhibition of soybean lipoxygenase and in vivo inhibition of the carrageenin-induced rat paw edema.Results: UMBELLIPRENIN did not show any significant antioxidant activity but exhibited a remarkable and potent inhibition against soybean lipoxygenase (IC50=0.0725 mM). This compound, in the in vivo anti-inflammatory test, could also inhibit the carrageenin induced paw edema significantly (39%).Conclusion: The observed inhibition of lipoxygenase may be a plausible mechanism for the potent cancer chemo preventive activity of UMBELLIPRENIN and may pose this compound as a valuable agent for the treatment of inflammatory diseases.

Objective: UMBELLIPRENIN is a prenylated compound, which belongs to the class of sesquiterpene coumarins. UMBELLIPRENIN is synthesized by various Ferula species plants used for food preparation or consumed as food such as Citrus Limon. Recently, UMBELLIPRENIN has been attracted much attention for its strong antitumor activities. Lung cancer is one of the most common causes of cancer related deaths in both men and women in most of countries. It is among the 10 most frequent cancers in Iranian population.Materials and Methods: To measure cell cytotoxity of UMBELLIPRENIN on human lung cancer cell lines including A549 and QU-DB, and murine lung cancer carcinoma LLC1, MTT cytotoxicity assay was performed.Results: IC 50 values for QU-DB, A549, and LLC1 were: (34.5 ± 5.9), (47 ± 5.2), and (47±3.1) Μm respectively, using MTT assay. Data represent the mean ± SD of at least two independent experiments done in triplicate.Conclusion: We found that UMBELLIPRENIN acts as an anti cancer compound in lung cancer cell lines in both human and mice cell lines, but their molecular targets are not clear. Characterizations of molecular targets of UMBELLIPRENIN using proteomics techniques are Underway.