Anti-lung Cancer and Anti-angiogenic Activities of New Designed Boronated Phenylalanine Metal Complexes.

BACKGROUND: Drug design and discovery studies still remain of great importance in the search for more convenient chemotherapeutic to avoid the drug resistance, systemic toxicity or the longterm side effects. OBJECTIVE: A series of mononuclear gold (III) and platinum (II) complexes based on 4-dihydroxyboryl- DL-phenylalanine (BPA) was designed and synthesized, for the first time, by using 2, 2'-dipyridyl (L1) and 4, 4'-diaminobibenzyl (L2) ligands. Characterization of the synthesized complexes was achieved by using 1H-NMR, IR, MS and elemental analyses. METHOD: MTT cell viability, endothelial tube formation, cancer cell colony formation and TRITCphalloidin cytoskeleton staining assays were performed on human umbilical vein endothelial (HUVEC) and human lung adenocarcinoma (A549) cells to establish the anticancer and anti-angiogenic activities of the complexes. It was determined that the organometallic complexes that include 2, 2'-dipyridyl ligand have higher antiproliferative activity than L2-based complexes in the micromolar range. Colony formation experiments showed that the anchorage-independent growth ability of A549s was significantly affected by the complexes in a concentration-dependent manner though L1-based complexes were more effective than L2-based ones. RESULTS: It was also clearly observed that the complexes have significant anti-angiogenic and cytoskeleton alterative activities. Consequently, the phenylalanine-based organometallic complexes seem to have anti-lung cancer and anti-angiogenic activities depending on the ligand type and a great potential in oncology drug development because phenylalanine amino acid has an ability to cross the cell membrane by using L-amino acid transport system. CONCLUSION: Design, synthesis and activity studies with amino acid analogs should be therefore increased to discover more efficient drugs to cure cancer diseases.

Promotion of Hair Growth by Traditionally Used Delphinium Staphisagria Seeds through Inducti on of Angiogenesis.

How the seeds of Delphinium staphisagria promote hair growth in humans is yet to be discovered. This lack of information leads us to the investigation of hair promoting effects of seeds of Delphinium staphisagria in-vitro. Extract prepared from the Seed of Delphinium staphisagria (ESDS) - traditionally used for hair loss treatment - was selected and tested for the cytotoxic and angiogenic potential in endothelial cells (HUVECs) and human keratinocytes (HaCaT) cells. The effects of extract was determined by using in-vitro colorimetric MTT [3-(4,5-dimethythiazol-2-yl)-2,5-diphenyltetrazolium bromide] cytotoxicity assay. To identify the compounds that induce angiogenesis, we applied matrigel capillary assay in-vitro using HUVECs. Vinegar and water extracts of D. staphisagria seeds significantly promoted the proliferation of human keratinocyte cells by 137, 139, 143, 149 and 147 % at the concentration of 100, 120, 200, 250 and 300 µg/mL compared with vehicle -treated control, respectively at 24 h. HUVECs viability remained the same with the control group at the concentration 1, 10, 20 and 40 µg/mL after 24 h. Results demonstrated that ESDS did not cause toxicity in human keratinocytes and endothelial cells, while inducing the angiogenic activity in-vitro. D. staphisagria seeds promote hair growth without overt cytotoxicity and through inducing angiogenesis. Based on the information from the traditional uses and our experimental results, D. staphisagria's seeds appear to be a good candidate for the promotion of hair growth.

Novel ferrocenyl-containing N-acetyl-2-pyrazolines inhibit in vitro angiogenesis and human lung cancer growth by interfering with F-actin stress fiber polimeryzation.

Cancer is a significant worldwide health problem generally because of lack of widespread and comprehensive early detection methods. Lung cancer is the leading cause of cancer deaths in men worldwide and the second leading cause of cancer deaths in women. To date, the available treatment regimens are not successful. For this reason, new targets for prevention and new agents for therapy need to be identified. The biological activities of some synthesized ferrocene-containing N-acetylated-2-pyrazoline compounds were studied for this article. Their cytotoxicity (by methyl thiazol tetrazolium assay), as well as apoptotic (by 4'6-diamidino-phenylindole and F-actin staining), antitumoral (colony-forming ability assay) and antiangiogenic activities (by tube formation), were evaluated for the first time on a human non-small-cell lung cancer (A549) cell line and a human umbilicial vein endothelial cell line. All compounds were cytotoxic, antitumoral and apoptotic against tumor cells in a dose-dependent manner. Compounds 2 and 3, which were noncytotoxic, could inhibit capillary vessel formation. Especially, N-acetyl-5-ferrocenyl-3-(2-thienyl)-2-pyrazoline (2) may be used in the development of therapeutic agents for angiogenic diseases and cancer.

Induction of apoptosis and inhibition of cell proliferation by the cyclooxgenase enzyme blocker nimesulide in the Ishikawa endometrial cancer cell line.

OBJECTIVES: Endometrial cancer remains a leading cause of death in women and therefore the development of new therapies is essential. The present study evaluated the effects of nimesulide alone, cisplatin alone, and combination of cisplatin and nimesulide on an Ishikawa cell line with respect to cytotoxicity and induction of apoptosis in vitro. STUDY DESIGN: Ishikawa cells were treated with increasing doses of nimesulide alone, cisplatin alone, and a combination of cisplatin and nimesulide. Subsequently their effects on cytotoxicity were investigated by MTT assay, while apoptosis was investigated by DAPI and JC-1 staining and caspase-3 colorimetric assays. RESULTS: 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay showed that nimesulide alone and combination of cisplatin and nimesulide have growth inhibitory effect on Ishikawa cells. Nimesulide alone and the combination of cisplatin and nimesulide induced apoptosis. Apoptosis induced by nimesulide might be related to caspase-3 activation. CONCLUSIONS: These results suggest that nimesulide treatment is as effective as cisplatin treatment in Ishikawa cells. The combination of cisplatin and nimesulide treatment is more effective than cisplatin alone in Ishikawa cells.

Assessment of anti-angiogenic and anti-tumoral potentials of Origanum onites L. essential oil.

Medicinal plants and culinary herbs with anti-angiogenic and little toxicity properties have gained importance. Non-toxic anti-angiogenic phytochemicals are useful in combating cancer by preventing the formation of new blood vessels to support the tumor growth. We have investigated the essential oil of Origanum onites L. (OOEO), for a possible anti-angiogenic activity. OOEO was analyzed by gas chromatography (GC) and gas chromatography-mass spectrometry (GC/MS). The anti-proliferative activities (by MTT assay, 3-(4,5-dimethyl-2-thiazol)-2,5-diphenyl-2H-tetrazolium bromide), anti-angiogenic activities (by tube formation assay), cell migration inhibiting capability (migration assay) and apoptotic potential (DAPI staining) of OOEO were evaluated on rat adipose tissue endothelial cells (RATECs) and 5RP7 (c-H-ras transformed rat embryonic fibroblasts) cells. Our results revealed that OOEO could markedly inhibit cell viability and induced apoptosis of 5RP7 cells and also could block in vitro tube formation and migration of RATEC. These results imply that OOEO having anti-angiogenic activity might be useful in preventing angiogenesis-related diseases and in combating cancer.