Seven organorhenium pentylcarbonate compounds (PC1-PC7) have been synthesized. DNA-binding studies of the PC-series compounds using electronic spectroscopy and gel electrophoresis suggest that the compounds presumably bind to DNA in an intercalative mode. The intrinsic binding constants for PC4, PC6, and PC7 were found to be 1.6 × 10(4), 3.9 × 10(4), and 4.2 × 10(4) M(-1), respectively. The X-ray structure determinations and density functional theory calculations indicate that the polypyridyl ligands in the compounds are nearly planar facilitating DNA binding through an intercalation mechanism. Cytotoxicity studies of 10 µM pentylcarbonate compounds against HTB-12 human astrocytoma brain cancer cells were studied for 48 h. It was observed that each of the pentylcarbonate compounds is active against the cancer cells. However, under analogous conditions, CRL-2005 rat astrocyte normal brain cells are not affected significantly.
PurposeBecause of the scarcity of suitable brain cancer drugs, researchers are frantically trying to discover novel and highly potent drugs free of side effects and drug-resistance. Rhenium compounds are known to be nontoxic and exhibit no drug resistance. For that reason, we have developed a series of novel rhenium acetylsalicylato (RAC or ASP) complexes to test their cytotoxicity on brain cancer cells. Also we have attempted to explore the DNAbinding properties of these compounds because many drugs either directly or indirectly bind to DNA.MethodsWe have treated the RAC series compounds on human astrocytoma brain cancer cell lines and rat normal brain astrocyte cells and determined the efficacy of these complexes through in vitro cytotoxicity assay. We carried out the DNA-binding study through UV titrations of a RAC compound with DNA. Also we attempted to determine the planarity of the polypyridyl ligands of the RAC series compounds using DFT calculations.ResultsRAC6 is more potent than any other RAC series compounds on HTB-12 human astrocytoma cancer cells as well as on Glioblastoma Multiforme D54 cell lines. In fact, The IC-50 value of RAC6 on HTB-12 cancer cells is approximately 2 μM. As expected, the RAC series compounds were not active on normal cells. The DFT calculations on the RAC series compounds were done and suggest that the polypyridyl ligands in the complexes are planar. The UV-titrations of RAC9 with DNA were carried out. It suggests that RAC9 and possibly all RAC series compounds bind to minor grooves of the DNA.ConclusionBecause of the very low activity of RAC6 on normal cells and low lC50 value of on astrocytoma (HTB-12) cell lines, it is possible that RAC6 and its derivatives may potentially find application in the treatment of brain cancers. The DFT calculations and UV titrations suggest that RAC series compounds either bind to DNA intercalatively or minor grooves of the DNA or both. However, it is highly premature to make any definite statement in the absence of other techniques.
In this report, investigations were done to study human GULP/ CED 6 genes role in presenting cancer cells to scavenger cells. CED 6 SiRNA was used to knock out the gene in Astrocytoma (HTB-12) cell lines to study its effects on expression of various "eat me" signals on these cells including Phosphatidyl serine (PtdSer) expression, nitric oxide (NO) signaling and Leukotrine B4 (LTB4) expression and Caspase 3 activation. Investigations were done by fluorescence microscopy techniques, ELISA assay and colorimetric assays using a standard microplate reader and spectrophotometer. Initial results showed all the above mentioned "eat me" signals were significantly decreased in CED 6 knock out cell lines. Therefore CED 6 gene must have a role in cancer cell clearance, pathway involved in the cross talk between CED 6 and other genes in this process is a matter of farther investigation.
Nano technology is a cutting edge science which is now effectively used in the field of cancer biology. Smart Flare gold nanoparticles are now used often for differential gene expression analysis. In this manuscript we are reporting the use of micro RNA miR 146a and onco gene EZH2 Smart Flare probes to study their expression in different prostate cancer cell lines and the effect of novel Rhenium compounds on these genes using a flow cytometer and a Fluorescence microscope. Our results showed this novel nanotechnology can be effectively used in cancer biology to successfully detect the effect of novel drugs on oncogenes and could be a very useful tool for next generation of cancer researchers.
Prostate cancer is one of the diseases worldwide that causes cancer-related deaths in men. Metformin is an antidiabetic drug that has been in use for over two decades for the treatment of Type II Diabetes mellitus (DM2). The purpose of this study was to evaluate the anti-proliferative property of metformin hydrochloride on androgen-sensitive, LNCAP and androgen-insensitive, PC-3 human prostate cancer cell lines at different concentrations (µM and mM) using 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay. Metformin hydrochloride displayed a stronger cytotoxicity on the androgen-insensitive PC-3 than on the androgen-sensitive human prostate cancer cell lines. For both cell lines, the antiproliferative activity of metformin hydrochloride was best displayed at 0.1 mM concentration with average cell death percentage of 60% after 120-hour exposure.
There is a need for additional biomarkers for the diagnosis and prognosis of prostate cancer. MicroRNAs are a class of non-protein coding RNA molecules that are frequently dysregulated in different cancers including prostate cancer and show promise as diagnostic biomarkers and targets for therapy. Here we describe the role of micro RNA 146 a (miR-146a) which may serve as a diagnostic marker for prostate cancer, as indicated from the data presented in this report. Also, a pilot study indicated differential expression of miR-146a in prostate cancer cell lines and tissues from different racial groups. This report provides a novel insight into understanding the prostate carcinogenesis.
Prostate cancer (PC) is the most common malignant cancer and the second leading cause of cancer‐related deaths in men. Approximately 18.9 out of 100,000 men per year die of prostate cancer. Common treatments such as androgen deprivation therapy (ADT,) surgical castration, and radiation therapy are used to counter PC; however, a proportion of patients relapse within a median of 2‐3 years with castration‐resistant prostate cancer (CRPC). In this study, combined effect of artesunate (ART) with paclitaxel (PTX) on human prostate cancer cell lines – LnCaP (androgen‐ dependent) and PC‐3 (androgen‐independent) were examined. In vitro anti‐proliferative (MTT) assay was used to assess the cytotoxic effects of ART, PTX, and in combination ratios 1:1, 1:2 and 2:1 on LnCaP and PC‐3 after 72‐ hour exposure. The IC50 values of 25.1 μM and 3.98 μM for ART and PXT on PC‐3 while the IC50 values of 2.13 μM and 0.05 μM on LnCaP were observed respectively. The average IC50 values when ART was combines with PXT were 0.499 μM and 0.084 μM on PC‐3 and LnCaP respectively. Overall, this study demonstrates that combining ART with PTX at different combination ratios has more effect on LnCaP than PC‐3 ‐ low IC50. In conclusion, combining ART with PTX displayed cytotoxicity regardless of the type of prostate cancer cell line. This may offer a promising new therapeutic option for the treatment of metastatic hormone‐refractory prostate cancer, aid in reducing cytotoxicity exerted by PTX alone and low prostate cancer mortality rate in men.
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