Extracts of Scrophularia frigida Boiss display potent antitumor effects in human breast cancer cells by inducing apoptosis and inhibition of expression of the human epidermal growth factor receptor 2.

Some species of the Scrophularia genus have been extensively used as a natural remedy for treatment of various medical conditions. The objective of this study was to evaluate the growth inhibitory activity of Scrophularia frigida Boiss extracts as well as to study the effect of the potent extracts on the induction of apoptosis and cell cycle arrest on human breast cancer cells. S. frigida Boiss extracts exhibited obvious inhibitory effects on the growth of cancer cells and induced apoptosis. It is suggested that the extracts exert their anti-proliferative effect through multiple implications such as suppressing growth, arresting the cell cycle, increased DNA fragmentation, downregulation of the expression of human epidermal growth factor receptor 2 and myeloid cell Leukemia-1, and upregulation of pro-apoptotic messenger RNAs like caspase-3 and caspase-9. Taken together, the results obtained indicate that S. frigida Boiss extracts may contain effective compounds that can be used as a therapeutic anticancer agent.

Effect of the menstrual cycle on inflammatory cytokines in the periodontium.

BACKGROUND AND OBJECTIVE: The effects of different levels of steroid hormones, as experienced during puberty, pregnancy and menopause, on the periodontium have been demonstrated, but changes in sex hormone levels during the menstrual cycle, and the influence of these changes on the periodontium, remain unresolved. The aim of this study was to investigate the effect of the menstrual cycle on the levels of interleukin-1beta (IL-1ß) and tumor necrosis factor-alpha (TNF-α) in gingival crevicular fluid and on periodontal clinical parameters, including the gingival bleeding index (GBI) and the modified gingival index (MGI), in periodontally healthy women. MATERIAL AND METHODS: Twenty-seven periodontally healthy women with a regular menstrual cycle were included in the study. Clinical parameters, including the GBI, the MGI and the simplified oral health index, were recorded during menstruation, ovulation and premenstruation phases (e.g. on days 1-2, 12-14 and 22-24, respectively) of the menstrual cycle. Gingival crevicular fluid and unstimulated saliva were collected, at each study phase, for assessment of IL-1ß, TNF-α, estrogen and progesterone. RESULTS: Both the GBI and the MGI increased significantly during the menstrual cycle, and were significantly higher during ovulation than during menstruation or premenstruation (p < 0.001). No significant change in the simplified oral health index was observed during the menstrual cycle ( p = 0.18). The levels of IL-1ß and TNF-α increased during the different phases of the menstrual cycle, but only the change in the TNF-α concentration was significant ( p < 0.05). CONCLUSION: This study indicated that changes occurring during the menstrual cycle influence the periodontium and induce inflammatory conditions.

Immunotherapy with tumor cell lysate-pulsed CD8α+ dendritic cells modulates intra-tumor and spleen lymphocyte subpopulations.

Using cellular adjuvants including dendritic cells (DCs) has provided a promising approach in immunotherapy of cancer. Our previous study showed that mice immunization with tumor cell lysate-pulsed DCs (TL-CD8α+DCs) could significantly suppress the tumor growth and increase mice survival. The aim of the present study was to investigate the impact of TL-CD8α+DC vaccine on intra-tumor and spleen lymphocyte subpopulations in tumor-bearing mice. ABalb/c mouse model of fibrosarcoma was used and changes in various lymphocyte subpopulations including CD4+, CD8+ and CD4+CD25+Foxp3+ T cells in mice immunized with TL-CD8α+ DCs were studied. The cytotoxic activity of the lymphocytes and tumor growth inhibitory rate were also measured. Immunotherapy with TL-CD8α+ DCs significantly enhanced both CD4+ and CD8+ lymphocytes, whereas decreased CD4+CD25+ Foxp3+ regulatory T cells as well as the tumor growth rate. There was also a decrease in the ratio of regulatory T cells to CD4+ and to CD8+ lymphocytes in both the tumor and spleen tissues as compared to that in the non-immunized control mice. Immunization with TL-CD8α+ DCs as well as CD8α+ DCs significantly increased the splenocytes cytotoxic activity by 45.1% and 18.2% of control, respectively. In conclusion, the current study indicated that TL-CD8α+ DCs can enhance tumor immunity against the fibrosarcoma by enhancing both the CD4+ and CD8+ lymphocytes and reducing regulatory T cells. This finding suggests the usefulness of TL-CD8α+DCs vaccine for cancer treatment.

Induction of apoptosis and G2 /M cell cycle arrest by Scrophularia striata in a human leukaemia cell line.

OBJECTIVES: Scrophularia striata Boiss (Scrophulariaceae) is a plant that grows in northeastern Iran; it has been used traditionally to treat various inflammatory disorders. This study was designed to investigate cytotoxic effects of S. striata extract, on the Jurkat human leukaemia cell line (T-cell leukaemia). MATERIALS AND METHODS: Phytochemical assay by thin layer chromatography and 2, 2 diphenyl-1-picryl-hydrazyl were used to evaluate main compounds and antioxidant capacity of the plant extract, respectively. Its inhibitory effect on Jurkat cells was evaluated by MTT assay. In addition, cell cycle distribution and apoptotic cell death were evaluated by propidium iodide and annexin V-FITC/ propidium iodide staining. RESULTS: These showed that the main components present in S. striata extract included flavonoids, phenolic compounds and phenyl propanoids. Treatment with extract was significantly cytotoxic to the tumour cell line. In addition, flow cytometry analysis indicated that S. striata extract induced cell cycle arrest in G2 /M phase and apoptosis of tumour cells. CONCLUSIONS: Results of the study indicated that S. striata extract could inhibit leukaemia cell proliferation by inducing G2 /M phase arrest and apoptosis.

Anticancer effects of various Iranian native medicinal plants on human tumor cell lines.

In this study the antineoplastic activity of methanolic extracts of six medicinal plants that are native to Iran, including Galium mite, Ferulago angulata, Stachys obtusicrena, Cirsium bracteosum and Echinophora cinerea was investigated. Different tumor cell lines were exposed to the extracts and cytotoxic analysis using MTT colorimetric assay was performed. Quantification of percentage of cells undergoing apoptotic changes by flow cytometry, and DNA fragmentation analysis on sensitive cell lines was then carried out. Results obtained indicated that almost all of the extracts more or less had the capacity to decrease the proliferation of tumor cells. Among the plants, the highest activity against K562 leukemia cell line was found for E. cinerea and C. bracteosum with IC50 less than 20 microg/ml followed by G. mite with IC50 of 39.8 microg/ml. F. angulata and E. cinerea, mostly inhibited Jurkat cells proliferation (IC50 less than 8 microg/ml). Fifty percent inhibition of Fen bladder cell carcinoma due to exposure to F. angulata and E. cinerea was found at concentrations of nearly 180 microg/ml. A549, a lung carcinoma cell, was mostly affected by S. obtusicrena (IC50 more than 200 microg/ml). In flow cytometry analysis, C. bracteosum, E. cinerea, F. angulata and S. obtusicrena extracts demonstrated no remarkable effects on the cell cycle profile of K562 and Jurkat cells. Moreover, in DNA fragmentation analysis of treated cells, no ladder formation was detected. In contrary, G. mite caused more than 40% apoptosis in the K562 and Jurkat cells. In DNA fragmentation analysis G. mite extract produced ladder formation in these cells. In conclusion, these results indicated that the extracts used in this study have anti tumor activity particularly against the leukemia cell lines and that apoptosis is the possible cause of cell death observed due to the extract of G. mite.