Green synthesis of silver nanoparticles using methanolic fruit extract of Aegle marmelos and their antimicrobial potential against human bacterial pathogens.

Plant-based synthesis of nanoparticles has generated worldwide interest because of cost-effectiveness, eco-friendly nature and plethora of applications. In the present investigation, antimicrobial potential of silver nanoparticles (AgNPs) of methanolic extract of Aegle marmelos fruit has been investigated. Agar well diffusion method was used for determining antimicrobial activity of solvent extracts (viz., petroleum ether, chloroform, acetone, methanol and aqueous), and AgNPs. Among these, methanolic extract of A. marmelos showed highest inhibitory activity against B. cereus (16.17 ±â€¯0.50 mm) followed by P. aeruginosa (13.33 ±â€¯0.62 mm) and E. coli. Phytochemical analysis of methanolic extract of A. marmelos revealed the presence of tannins, saponins, steroids, alkaloids, flavonoids, and glycosides. AgNPs synthesized using A. marmelos methanolic extract, characterized by UV-Visible spectroscopy, atomic force microscopy, dynamic light scattering, and X-ray diffraction showed a peak at 436 nm and size ranged between 159 and 181 nm. Evaluation of the antimicrobial potential of green synthesized AgNPs recorded the highest inhibitory activity against B. cereus (19.25 ±â€¯0.19 mm) followed by P. aeruginosa (16.50 ±â€¯0.30 mm) and S. dysentriae. The minimum inhibitory concentration (MIC) of synthesized AgNPs was found to be in the range of 0.009875-0.0395 mg/100 µl which was quite lower than the MIC of crude extract i.e. 0.0781-0.3125 mg/100 µl. The results obtained indicated that the different crude extracts of A. marmelos plant as well as AgNPs have a strong and effective antimicrobial potential that provide a marvelous source for the development of new drug molecules of herbal origin which may be used for the welfare of humanity.

Iron chelators induce autophagic cell death in multiple myeloma cells.

We examined the antineoplastic effects of the iron chelators, deferasirox and deferoxamine in multiple myeloma cell lines as well as primary myeloma cells. These iron chelators showed marked antiproliferative activity as well as cytotoxicity toward myeloma cell lines and deferasirox was cytotoxic to bone marrow plasma cells from myeloma patients. We also demonstrate that autophagy induced by iron deprivation is the dominant mechanism that mediates the cytotoxicity of iron chelators in multiple myeloma. Exposure to iron chelators led to repression of mTOR signaling as evidenced by decreased phosphorylation of its target p70S6 kinase. Iron chelation, in particular with deferasirox has the potential to be readily translated to a clinical trial for multiple myeloma.

Indirubin derivatives induce apoptosis of chronic myelogenous leukemia cells involving inhibition of Stat5 signaling.

Indirubin is the major active anti-tumor component of a traditional Chinese herbal medicine used for treatment of chronic myelogenous leukemia (CML). While previous studies indicate that indirubin is a promising therapeutic agent for CML, the molecular mechanism of action of indirubin is not fully understood. We report here that indirubin derivatives (IRDs) potently inhibit Signal Transducer and Activator of Transcription 5 (Stat5) protein in CML cells. Compound E804, which is the most potent in this series of IRDs, blocked Stat5 signaling in human K562 CML cells, imatinib-resistant human KCL-22 CML cells expressing the T315I mutant Bcr-Abl (KCL-22M), and CD34-positive primary CML cells from patients. Autophosphorylation of Src family kinases (SFKs) was strongly inhibited in K562 and KCL-22M cells at 5 µM E804, and in primary CML cells at 10 µM E804, although higher concentrations partially inhibited autophosphorylation of Bcr-Abl. Previous studies indicate that SFKs cooperate with Bcr-Abl to activate downstream Stat5 signaling. Activation of Stat5 was strongly blocked by E804 in CML cells. E804 down-regulated expression of Stat5 target proteins Bcl-x(L) and Mcl-1, associated with induction of apoptosis. In sum, our findings identify IRDs as potent inhibitors of the SFK/Stat5 signaling pathway downstream of Bcr-Abl, leading to apoptosis of K562, KCL-22M and primary CML cells. IRDs represent a promising structural class for development of new therapeutics for wild type or T315I mutant Bcr-Abl-positive CML patients.