Synthesis and cytotoxic activities of organometallic Ru(II) diamine complexes.

A series of mono and bimetallic ruthenium(II) arene complexes bearing diamine (Ru1-6) were prepared and fully characterized by 1H, 13C, 19F, and 31P NMR spectroscopy and elemental analysis. The crystal structure of the bimetallic complex (Ru5) was determined by X-ray crystallography. Monometallic analogues (Ru1-3) were synthesized to investigate the contributions of ruthenium and the other organic groups (aren, ethylenediamine, butyl) to the activity. The electrochemical behaviors of mono and bimetallic complexes were obtained from the relationship between cyclic voltammetry (CV) and the biological activities of the compounds. The cytotoxic activities of the complexes (Ru1-6) were tested against wide-scale cancer cell lines, namely HeLa, MDA-MB-231, DU-145, LNCaP, Hep-G2, Saos-2, PC-3, and MCF-7, and normal cell lines 3T3-L1 and Vero. Diamine Ru(II) arene complexes have unique biological characteristics and they are promising models for new anticancer drug development. MTT analysis reveals that each synthesized Ru complex showed cytotoxic activity towards the different cancer cells. In particular, three Ru complexes (Ru3, Ru5 and Ru6) showed less toxic effects on the cancer cells than the others. These novel Ru complexes affected both cancer and normal cell lines. As they had a toxic effect on the cells, the dosage applied should be tested before being used for in vivo applications. Cytotoxicity tests have shown that the bimetallic complex Ru6 was effective on all cancer cells. The effect of bimetallic enhancement on cancer cell lines, the systematic variation of the intermetallic distance and the ligand donor properties of the mono and bimetallic complexes were explored based on the cytotoxic activity. The interaction with FS-DNA and the stability/aquation of the complexes (Ru3 and Ru6) were investigated with 1H NMR spectroscopy. The binding modes between the complexes (Ru3 and Ru6) and DNA were investigated via UV-Vis spectroscopy.

The effects of tramadol on cancer stem cells and metabolic changes in colon carcinoma cells lines.

Opioids are widely used in the treatment of cancer related pain. They mainly exert their effects on opioid receptors. The most common opioid in the treatment of pain is morphine. Previous studies show that they may have effects on cancer cell behavior. These may include apoptosis, angiogenesis, invasion, inflammation and immune reactions. Tramadol, also an opioid is widely used in the treatment of cancer pain and is not well studied in cancer behavior. We aimed to investigate the effects of tramadol on cancer stem cells and metabolic changes in colon carcinoma cells. We used Colo320 (ATCC, CCL-220), Colo741 (ECACC, 93052621) and HCT116 (ATCC, CCL-247) colon cancer cell lines. CD133 was considered colon cancer stem cell marker and used to sort CD133+ and CD133- cells by magnetic cell sorting. MTT (mitochondria-targeted therapeutics) technique was used to detect tramadol's cytotoxic effect on cells in the study groups. Cells were treated with 1 mg/kg, 1.5 mg/kg and 2 mg/kg tramadol for 24 h at 37 °C and 5% CO2.Caspase-3, Ki-67, Bcl-2 and VGEF distributions were performed using indirect immunoperoxidase staining for immunohistochemical analysis. The study showed that tramadol has triggering effect on apoptosis in Colo320 colon cancer stem cells.

In vitro investigation of the effect of matrix molecules on the behavior of colon cancer cells under the effect of geldanamycin derivative.

The chaperone-binding drug, 17-allylamino-17-demethoxygeldanamycin, has recently come into clinical use. It is a derivative of geldanamycin, an ansamycin benzoquinone antibiotic with anti-carcinogenic effect. Understanding the effect of this drug on the cancer cells and their niche is important for treatment. We applied 17-allylamino-17-demethoxygeldanamycin to colon cancer cell line (Colo 205) on matrix molecules to investigate the relationship of apoptosis with terminal deoxynucleotidyl transferase dUTP nick end labeling immunocytochemistry and related gene expression. We used laminin and collagen I for matrix molecules and vascular endothelial growth factor for angiogenic structure. We also examined apoptosis-related signaling pathway including mitochondrial proteins, cytochrome c, Bcl-2, caspase-9, Apaf-1 expression using real-time polymerase chain reaction. There was clear effect of 17-allylamino-17-demethoxygeldanamycin that killed more cells on tissue culture plastic compared to matrix molecules. The IC50 value was 0.58 µg/mL for tissue culture plastic compared with 0.64 µg/mL for laminin and 0.75 µg/mL for collagen I. The analyses showed that more cells on matrix molecules underwent apoptosis compared to that on tissue culture plastic. Apoptosis-related gene expression was similar in which Bcl-2 expression decreased and proapoptotic gene expression of the cells on matrix molecules increased compared to that on tissue culture plastic. However, the application of 17-allylamino-17-demethoxygeldanamycin was more effective for the cells on collagen I compared to the cells on laminin. There was also a decrease in angiogenesis as shown by the vascular endothelial growth factor staining. This was more pronounced by coating of the tissue culture plastic with matrix molecules. Our results supported the anti-cancer effect of 17-allylamino-17-demethoxygeldanamycin, and this effect depended on matrix molecules. This effect occurs through apoptosis, and related genes were also altered. All these genes may serve for novel target under the effect of matrix substrate. However, correct interpretation of the results requires further studies.

Potential Clinical Use of Differentiated Cells From Embryonic or Mesencyhmal Stem Cells in Orthopaedic Problems.

Stem cells are classified by their tissue source. Embryonic stem cells that are derived from the inner cell mass of blastocyst stage embryos are highly proliferative in their undifferentiated state. A multipotent type of mesenchymal stem cells is isolated from various types of tissues such as bone marrow, fat tissue etc. The dynamics of embryonic and adult stem cell cycles are profoundly dissimilar from the culture of stem cells. After improving the culture conditions and differentiation potentials, differentiated stem cells are the first cells to be preferred in modern regenerative medicine and tissue engineering. This review article focuses on the cell-based therapy of orthopedic problems. We explore the challenges associated with bone repair and regeneration using embryonic or mesenchymal stem cells that are in undifferentiated or/and differentiated condition. This paper also discusses optimizing the best cell type, differentiation condition and using them on bone tissue engineering for future investigations.

Potential clinical use of differentiated cells from embryonic or Mesenchymal stem cells in orthopeadic problems.

Stem cells are classified by their tissue source. Embryonic stem cells that derived from inner cell mass of blastocyst stage embryos are highly proliferative in their undifferentiated state. A multipotent type of mesenchymal stem cells isolated from different type of tissues such as bone marrow, fat tissue etc. The dynamics of embryonic and adult stem cell cycles are profoundly dissimilar than the culture of stem cells. After improving the culture conditions and differentiation potentials, differentiated stem cells are the first cells to be preferred in modern regenerative medicine and tissue engineering. This review article focuses on the cell-based therapy on orthopedic problems. We explore the challenges associated with bone repair and regeneration using embryonic or mesenchymal stem cells that use undifferentiated or/and differentiated condition. This paper also discusses optimizing the best cell type, differentiation condition and using them on bone tissue engineering in future investigation.

Random/aligned electrospun PCL/PCL-collagen nanofibrous membranes: comparison of neural differentiation of rat AdMSCs and BMSCs.

In this study, the aligned (A) and randomly oriented (R) polycaprolactone (PCL-A and PCL-R) and PCL/collagen (PCL/Col-A and PCL/Col-R) nanofibers were electrospun onto smooth PCL membranes (PCLMs) prepared by solvent casting. In order to investigate the effects of chemical composition and nanotopography of fibrous surfaces on proliferation and on neural differentiation of mesenchymal stem cells (MSCs), adipose and bone marrow-derived rat MSCs (AdMSCs and BMSCs) were cultivated in suitable media i.e. inducing medium containing basic fibroblast growth factor (bFGF) and epidermal growth factor (EGF), and cell maintenance medium (CMM). BMSCs adhered and proliferated on all nanofibrous membranes more efficiently than AdMSCs. PCL/Col-A was found as the most convenient surface supporting proliferation in both cell types. Immunofluorescence staining indicated that BMSCs and AdMSCs are prone for differentiation to oligodendrocytes more than they differentiate to other neuronal cell types. PCL-A nanofibrous membranes supported differentiation of MSCs to O4(+) (an oligodendrocytes surface antigen) cells in both culture media. The intensity of immunoreactivity of O4(+) cells differentiated from BMSCs on PCL-A was highest when compared with the other groups (p < 0.001). Some BIII-T signed neural cells were investigated on PCL-A nanofibrous membranes, but the intensity of immunoreactivity was lower than that of O4(+) cells. In conclusion, this study can be evaluated to establish the cell therapy strategies in neurodegenerative disorders, which are relevant to oligodendrocyte abstinence using BMSCs or AdMSCs on aligned nanofibrous membranes.