Antitumor activity of vanadocene Y and its selenocyanate derivative in xenografted caki-1 tumors in mice

The para-methoxybenzyl-substituted vanadocene dichloride (Vanadocene Y) (1) and its diselenocyanate (Selenocyanato-Vanadocene Y) (2) were tested in vitro in an anti-angiogenesis assay against human umbilical vein endothelial cells (HUVEC) delivering IC50 values of 0.92 ± 0.03 μM (1) and 37 ± 11 μM (2). In a cytotoxicity assay against the human renal cancer cells, CAKI-1, the compounds demonstrated IC50 values of 0.55 ± 0.09 μM (1) and 0.25 ± 0.03 μM (2). Then both compounds were given at their maximum tolerable dose, MTD, of 20 mg/kg/d (1) or 40 mg/kg/d (2) on four consecutive days or at 50% of the MTD on five consecutive days per week for three weeks to overall four cohorts of eight CAKI-1 tumor-bearing female NMRI:nu/nu mice each, while a further cohort was treated with solvent only. Both MTD-treated mouse cohorts showed a statistically significant tumor growth reduction with respect to the solvent-treated control group with an optimal T/C value of 47% on day 39 of the experiment. Immunohistological analysis revealed that the expression of the proliferation marker Ki-67 was reduced due to long-term treatment with 2.     

Co-localization of PCNA, VCAM-1 and caspase-3 with nestin in xenografts derived from human anaplastic astrocytoma and glioblastoma multiforme tumor spheres

The cancer stem cell hypothesis proposes that tumors contain a small subset of cancer cells, the cancer stem cells, which constitute a reservoir of self-sustaining cells with the exclusive ability to self-renew and maintain the tumor. Markers that define cancer stem cells that are capable of recapitulating brain tumors as xenografts in mice has not been described. We investigated the relationship between expression of nestin and that of PCNA, VCAM-1 and caspase-3 in the xenografts developed from human anaplastic astrocytoma and glioblastoma tumor-derived spheres in the brain of nude mouse. Xenografts obtained from astrocytoma tumor stem cells (ATSC) and glioblastoma tumor stem cells (GTSC) have showed a large number of cells positive for both PCNA and the nestin, demonstrating that nestin expressing cells have a high rate of proliferation. Xenografts from GTSC showed heterogeneous staining pattern with cells that express both nestin and VCAM-1, whereas others cells remained complete negative. In this case it was noticed that most tumor cells with large or multinucleated nuclei coexpress nestin and VCAM-1. In xenografts from ATSC most cells positive for nestin express VCAM-1 and in this case the two proteins appear to occupy the same cytoplasmic region. Both GTSC and ATSC derived xenografts showed cells positive for both caspase-3 and for nestin detected mainly as single cells and as cell clusters located near or around a blood vessel.     

A InIII‐MOF with Imidazole Decorated Pores as 5‐Fu Delivery System to Inhibit Colon Cancer Cells Proliferation and Induce Cell Apoptosis in vitro and in vivo

A new nontoxic porous In^III‐based metal‐organic framework [In(Hpbic)(pbic)](DMF)₂ ( 1 ) (DMF = N,N‐dimethylacetamide) was successfully prepared with 2‐(pyridin‐4‐yl)‐1H‐benzo[d]imidazole‐5‐carboxylic acid (H₂pbic) as organic linker via a solvothermal process. Further, the nanostructure 1 could be obtained via a green grinding method. Nitrogen adsorption measurements revealed the presence of micropores as well as moderate high BET surface areas in the activated nanostructure 1 ( 1a ). The drug loading experiment shows that 5‐fluorouracil (5‐Fu) is preferentially captured into the pore of the nanostructure 1a with a loading capacity of 32.6 %. Meanwhile, the controlled release of 5‐Fu in a simulated human body with liquid phosphate‐buffered saline solution was realized. In addition, the Cell Counting Kit‐8 (CCK‐8) assay was conducted to determine the inhibitory effect of 5‐Fu@ 1a on human colon cancer cell SW60 viability and proliferation, the results indicated the excellent anti‐cancer activity of 5‐Fu@ 1a in vitro. To reveal the related mechanism, the Annexin V‐FITC/PI assay and reactive oxygen species (ROS) level detection was carried out after 5‐Fu@ 1a treatment. Finally, the in vivo xenograft model was constructed in mice, the tumor volume, and mice body weight were recording at indicated time. The in vivo results suggested the significant inhibitory activity of 5‐Fu@ 1a in mice.