Vikram Dhuna

Evaluation of hydro-alcoholic extract of Eclipta alba for its anticancer potential: An in vitro study

ETHNOPHARMACOLOGICAL RELEVANCE Eclipta alba is traditionally used as hepatoprotective agent. The study was designed to explore its antiproliferative activity on liver and other related cancer. AIM OF THE STUDY The present study was designed to assess and establish the role of Eclipta alba as anti-cancer agent using HepG2, C6 glioma and A498 cell lines as model system. MATERIALS AND METHODS Antiproliferative and cytotoxic effects of the Eclipta alba hydroalcoholic extract (EAE) was determined using MTT assay. The expression level of NF-kB was analysed by western blotting and RT PCR. Gelatin zymography was done for gelatinase matrix metalloproteinases (MMP-2 and 9) analysis. RESULTS EAE inhibited the cell proliferation in dose dependent manner in HepG2, A498 and C6 glioma cell lines with an IC50 of 22±2.9, 25±3.6 and 50±8.7 μg/ml, respectively. The expression of MMP (2 and 9) was down-regulated with EAE treatment. DNA damage was observed following 72h of extract treatment, leading to apoptosis. Additionally, the expression level of NF-kB was evaluated with western blotting and RT-PCR and was found to be down-regulated/inactivated. CONCLUSIONS The data establish the existence of anti-proliferative, DNA damaging and anti-metastasis properties in EAE which is yet unexplored and hold high therapeutic impact.

Role of glass structure in defining the chemical dissolution behavior, bioactivity and antioxidant properties of zinc and strontium co-doped alkali-free phosphosilicate glasses.

We investigated the structure-property relationships in a series of alkali-free phosphosilicate glass compositions co-doped with Zn(2+) and Sr(2+). The emphasis was laid on understanding the structural role of Sr(2+) and Zn(2+) co-doping on the chemical dissolution behavior of glasses and its impact on their in vitro bioactivity. The structure of glasses was studied using molecular dynamics simulations in combination with solid state nuclear magnetic resonance spectroscopy. The relevant structural properties are then linked to the observed degradation behavior, in vitro bioactivity, osteoblast proliferation and oxidative stress levels. The apatite-forming ability of glasses has been investigated by X-ray diffraction, infrared spectroscopy and scanning electron microscopy-energy-dispersive spectroscopy after immersion of glass powders/bulk in simulated body fluid (SBF) for time durations varying between 1h and 14 days, while their chemical degradation has been studied in Tris-HCl in accordance with ISO 10993-14. All the glasses exhibit hydroxyapatite formation on their surface within 1-3h of their immersion in SBF. The cellular responses were observed in vitro on bulk glass samples using human osteosarcoma MG63 cell line. The dose-dependent cytoprotective effect of glasses with respect to the concentration of zinc and strontium released from the glasses is also discussed.

A novel antiproliferative and antifungal lectin from Amaranthus viridis Linn seeds.

A lectin from the seeds of Amaranthus viridis Linn has been purified by affinity chromatography on asialofetuin-linked amino activated silica. Amaranthus viridis lectin (AVL) has a native molecular mass of 67 kDa. It is a homodimer composed of two 36.6 kDa subunits. The lectin gave a single band in non-denaturing PAGE at pH 4.5 and pH 8.3 and a single peak on HPLC size exclusion and cation exchange columns. The purified lectin was specific for both T-antigen and N-acetyl-D-lactosamine, markers for various carcinomas, in addition to N-acetyl-D-galactosamine, asialofetuin and fetuin. This lectin reacted strongly with red blood cells (RBCs) from human ABO blood groups and rat. It also reacted with rabbit, sheep, goat and guinea pig RBCs. The lectin is a glycoprotein having no metal ion requirement for its activity. Denaturing agents such as urea, thiourea and guanidine-HCl had no effect on its activity when treated for 15 minutes. AVL showed significant antiproliferative activity towards HB98 and P388D1 murine cancer cell lines. It also exerted antifungal activity against phytopathogenic fungi Botrytis cincerea and Fusarium oxysporum but not against Rhizoctonia solani, Trichoderma reesei, Alternaria solani and Fusarium graminearum.

The synthesis, spectroscopic characterization and anticancer activity of new mono and binuclear phosphanegold(I) dithiocarbamate complexes

A new series of mononuclear [t-Bu3PAuS2CN(C7H7)2] (1), and binuclear [(DPPM)Au2(S2CN(CH3)2)2] (2), [(DPPM)Au2(S2CN(C2H5)2)2] (3) and [(DPPM)Au2(S2CN(C7H7)2)2] (4) [where DPPM = 1,1-bis(diphenylphosphino)methane, S2CN(CH3)2 = dimethyldithiocarbamate, S2CN(C2H5)2 = diethyldithiocarbamate and S2CN(C7H7)2 = dibenzyldithiocarbamate] gold(I) complexes have been prepared by reacting gold(I) precursors and dialkyl–diaryl dithiocarbamate ligands. The complexes were characterized by an analytical technique and spectroscopic methods such as CHNS analysis, FTIR spectroscopy; 1H, 13C and 31P NMR measurements. The molecular structure of the [t-Bu3PAuS2CN(C7H7)2] (1) complex was determined by X-ray diffraction. The gold(I) complexes (2 and 3) were found particularly to be better potent in vitro cytotoxic agents in comparison to cisplatin against HeLa, HCT15 and A549 cancer cell lines. These metal complexes could serve as attractive anticancer agents for the development of novel therapeutic strategies and to treat cervix, lung and colon cancers.

Tetrakis(thione)platinum(II) complexes: synthesis, spectroscopic characterization, crystal structures, and in vitro cytotoxicity

A new series of platinum(II) complexes based on thione ligands with general formula [Pt(thione)4]X2 (X− = Cl−, NO3−) has been synthesized and characterized using CHNS elemental analysis, infrared, 1H and 13C solution-state NMR as well as 13C and 15N solid-state NMR spectroscopy, and X-ray crystallography. The spectroscopic methods confirm the coordination of Pt(II) with thiocarbonyl groups via sulfur of the thione ligands. The X-ray structures showed a distorted square planar geometry for 1, [Pt(MeImt)4]Cl2 (MeImt = N-Methylimidazolidine-2-thione) while the hydrogen bonding interactions in 7, [Pt(iPrImt)4](NO3)2·0.6(H2O) induce a bent see-saw distortion relative to the ideal square planar geometry. The in vitro cytotoxicity studies showed that 2, [Pt(EtImt)4]Cl2 is generally the most effective, a two-fold better cytotoxic agent than cisplatin and carboplatin against MCF7 (human breast cancer). Graphical abstract

Some new [(thione)2Au(diamine)]Cl3 complexes: synthesis, spectroscopic characterization, computational and in vitro cytotoxic studies.

Recent advances in oncology are focused on developing new complexes of gold(III) with various ligands that show augmented anti-proliferative potential and reduced toxicity as compared to cis-platin. In this study, new Au(III) complexes of the type [(thione)2Au(diamine)]Cl3 are reported, where thione=1,3-imidazolidine-2-thione (Imt), 1,3-Diazinane-2-thione (Diaz) and diamine=1,2-diaminoethane (en), 1,3-diaminopropane (pn) or 1,4-diaminobutane (bn). The solid state IR as well as (13)C and (15)N NMR data indicate that Au(III) center is bonded via sulfur of thiocarbonyl SC site of the thiones and also chelated by the diamines from the trans side of coordinated thiones. Spectroscopic data are evaluated by comparisons with calculated data from the built and optimized structure by GAUSSIAN 09 at the RB3LYP level with LanL2DZ bases set. These new Au(III) complexes based on mixed thione and diamine ligands are very similar to the square planar structure of tetracoordinate [Au(en)2]Cl3complex. In this study, cytotoxicity data for these gold(III) complexes against C6 glioma cell lines are also reported, and the results indicate some complexes have cytotoxicity comparable to cis-platin.

Bacopa monnieri extracts prevent hydrogen peroxide-induced oxidative damage in a cellular model of neuroblastoma IMR32 cells

Neurodegenerative diseases are the consequences of imbalance between the production of oxidative stress and its nullification by cellular defense mechanisms. Hydrogen peroxide (H2O2), a precursor of deleterious reactive oxygen species, elicits oxidative stress, resulting in severe brain injuries. Bacopa monnieri is well known for its nerve relaxing and memory enhancing properties. The present study was designed to evaluate the protective effects of extracts from Bacopa monnieri against H2O2 induced oxidative stress using a cellular model, neuroblastoma IMR32 cell line. The protective potential of methanolic, ethanolic, and water extracts of B. monnieri (BM-MEx, BM-EEx, and BM-WEx) was evaluated using MTT assay. Although, all the B. monnieri extracts were found to protect cells against H2O2-mediated stress but BM-MEx showed significantly greater protection. UPLC analysis of BM-MEx revealed various polyphenols, including quercetin, catechin, umbelliferone, and caffeic acid predominance. Further, BM-MEx was found to possess considerable greater neuroprotective potential in comparison to the standard polyphenols such as quercetin, catechin, umbelliferone, and caffeic acid. The levels of antioxidant enzymes were significantly elevated after the pretreatment of BM-MEx and quercetin. The expression levels of oxidative stress markers, such as NF200, HSP70, and mortalin, were significantly alleviated after the pretreatment of BM-MEx as shown by immunofluorescence and RT-PCR. In conclusion, the present study demonstrated the protective effects of BM-MEx, suggesting that it could be a candidate for the development of neuropathological therapeutics.