Background: Currently, nanomaterials (NMs) research and development is at a fastest pace due to the enhanced implication in different areas of applications. The synthesis of such NMs through biosynthesis methods is gaining much importance because of low cost involved and environment-friendly approach. In this present study, the nanoparticles (NPs) are synthesized using a medicinal plant, with anticancer properties so as to incorporate the therapeutic activity within the NPs, such that the NPs will have the attributes of NMs alongside the phytoactivity. Results: The synthesis of gold nanoparticles (AuNPs) using Graviola, the fruit of Annona muricata (Ramaphal fruit) commonly referred as Mullu seetha fruit (Tamil), was successfully carried out. The initial confirmations of the NPs were using UV-vis spectra, which showed the characteristic peak for the NPs. HRSEM analysis gave an insight on the size and morphology of the NPs. The zeta potential was measured to check the stability of the NPs. The cytotoxicity was carried out in VERO cell line and anticancer study in Hep2 liver cancer cell line. The surface plasmon resonance (SPR) band showed the characteristic peak at 536 nm for the AuNPs. In SEM micrographs, the size was ranging between 20 and 30 nm, on an average of 15 nm with spherical morphology. On the various tested concentrations in VERO cell line, the nanoparticles were non-toxic to the cells. The anticancer study gave an IC50 value at 10.94 μg/ml. Conclusions:The NPs showed anticancer activity in treated Hep2 liver cancer cell line and as well as commendable non-toxic effect on normal VERO cell line. The results pose a positive impact to expand further studies in the development of potential drug molecules to tackle the disease of interest.
Aims: Indian folk medicine has been in practice from time immemorial. Traditional medicine interconnects our body with nature for a healthy living. The naturally occurring antimicrobials in food vary in their efficacy and function, toxicology, safety and mechanism of action against microorganisms. Methodology and Results:The study revitalizes the traditional system of medicine in order to achieve self reliance in health care and health for all by analyzing the antimicrobial property of aqueous extracts of aloevera (Aloevera barbedensis), carrot (Daucus carota), Indian gooseberry (Emblica officinalis), honey and pomegranate (Punica granatum), and to assess the reason for inhibition of growth of pathogenic organisms by DNA and protein analysis. Various aqueous extracts showed inhibition to microrganisms like Escherichia coli, Pseudomonas aeruginosa, Salmonella typhi, Shigella flexineri and Staphylococcus aureus.Conclusion significance and impact of study: The study also formulated and standardized a nourishing health drink and salad using the tested foods and estimated their shelf life and nutritive value. The health drink and salad had a low protein, low fat and moderate carbohydrate content. Therapeutically this drink and salad can be used to treat obesity.
It has been previously stated that gold nanoparticles have been successfully synthesized using various green extracts of plants. The synthesized gold nanoparticles were characterized under scanning electron microscopy and EDX to identify the size of the nanoparticles. It was found that the nanoparticles were around 30 nm in size, which is a commendable nano dimension achieved through a plant mediated synthesis. The nanoparticles were further studied for their various applications. In the current study, we have made attempts to exploit the anticancer ability of the gold nano particles. The nanoparticles were studied against MCF 7 breast cancer cell lines. The results obtained from the studies of anticancer activity showed that gold nanoparticles gave an equivalent good results, in par with the standard drugs against cancer. The AuNP's proved to be efficient even from the minimum concentrations of 2 lg/ml, and as the concentration increased the anticancer efficacy as well increased.
Enhancer of Zeste Homolog 2 (EZH2) is the histone lysine methyltransferase (HKMT) component of the Polycomb Repressive Complex 2 (PRC2). In conjunction with other members of the complex, EZH2 represses gene expression through methylation of histone H3 on lysine 27 (H3K27). EZH2 overexpression is implicated in tumor progression and correlates with poor prognosis in several tumor types and enzymatic hyperactivity of EZH2 has been linked to aberrant repression of tumor suppressor genes in diverse cancers. Recently, direct inhibition of EZH2 HKMT activity by small molecules has been shown to be effective in inhibiting the proliferation of EZH2 mutant diffuse large B-cell lymphoma (DLBCL) cell lines and the growth of tumors in EZH2 mutant DLBCL xenografts. We have identified and optimized a series of small molecule EZH2 inhibitors that is structurally distinct from previously published chemotypes. CPI-169, a representative compound from that effort, inhibits the catalytic activity of PRC2 with an IC50 of < 1nM, decreases cellular levels of H3K27me3 with an EC50 of 70 nM, and triggers cell cycle arrest and apoptosis in a variety of cell lines. Importantly, compound treatment triggers a sequence of downstream functional consequences of EZH2 inhibition whereby apoptosis is not induced before ten days of continuous target engagement. Administered subcutaneously at 200 mpk twice daily (BID), CPI-169 is well tolerated in mice with no observed toxic effect or body weight loss. In the present study we show that CPI-169 treatment led to tumor growth inhibition (TGI) of an EZH2 mutant KARPAS-422 DLBCL xenograft. The TGI is proportional to the dose administered and to the reduction of the pharmacodynamic marker H3K27me3. The highest dose, 200 mpk, BID led to complete tumor regression. Since CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone) is the standard treatment of advanced DLBCL, we were interested in combining a suboptimal dose of CPI-169 (100 mpk, BID) with a single dose of CHOP in the KARPAS-422 model. After a week of combinatorial treatment the tumors rapidly regressed and became unpalpable. Four weeks after the last dose only a single mouse presented a palpable tumor. The immunohistochemical analysis of tumor samples revealed a strong correlation between the global decrease of H3K27me3, the decrease in the proliferation marker Ki-67 and the increase in cleaved-caspase 3 positive cells. In conclusion, we identified a strong synergistic anti-tumor activity between the standard of care CHOP and CPI-169, a distinct EZH2 inhibitor in an in vivo model of DLBCL. Citation Format: Vidya Balasubramanian, Priya Iyer, Shilpi Arora, Patrick Troyer, Emmanuel Normant. CPI-169, a novel and potent EZH2 inhibitor, synergizes with CHOP in vivo and achieves complete regression in lymphoma xenograft models. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1697. doi:10.1158/1538-7445.AM2014-1697
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