Entity

Time filter

Source Type

Pune, India

Shiradkar M.,Lupin Research Park | Pawankumar G.,Nethaji Institute of Pharmaceutical science
International Journal of Pharma and Bio Sciences | Year: 2011

This project was designed with the objective of investigating glucose lowering potential, anti-mutagenic activity and anti-fertility activity of Cassia auriculata bark extract in the diabetic animals. The albino rats were treated with methanolic extract. The extracts were found to posses promising anti-diabetic, antimutagenic and anti-fertility activities. Source


Konduri S.D.,Roswell Park Cancer Institute | Konduri S.D.,Cancer Research Institute | Medisetty R.,Roswell Park Cancer Institute | Liu W.,Roswell Park Cancer Institute | And 14 more authors.
Proceedings of the National Academy of Sciences of the United States of America | Year: 2010

Estrogen receptor α (ERα) plays an important role in the onset and progression of breast cancer, whereas p53 functions as a major tumor suppressor. We previously reported that ERα binds to p53, resulting in inhibition of transcriptional regulation by p53. Here, we report on the molecular mechanisms by which ERα suppresses p53's transactivation function. Sequential ChIP assays demonstrated that ERα represses p53-mediated transcriptional activation in human breast cancer cells by recruiting nuclear receptor core-pressors (NCoR and SMRT) and histone deacetylase 1 (HDAC1). RNAi-mediated down-regulation of NCoR resulted in increased endogenous expression of the cyclin-dependent kinase (CDK)-inhibitor p21Waf1/Cip1 (CDKN1A) gene, a prototypic transcriptional target of p53. While 17β-estradiol (E2) enhanced ERα binding to p53 and inhibited p21 transcription, antiestrogens decreased ERα recruitment and induced transcription. The effects of estrogen and antiestrogens on p21 transcription were diametrically opposite to their known effects on the conventional ERE-containing ERα target gene, pS2/TFF1. These results suggest that ERα uses dual strategies to promote abnormal cellular proliferation: enhancing the transcription of ERE-containing proproliferative genes and repressing the transcription of p53-responsive antiproliferative genes. Importantly, ERα binds to p53 and inhibits transcriptional activation by p53 in stem/progenitor cell-containing murine mammospheres, suggesting a potential role for the ER-p53 interaction in mammary tissue homeostasis and cancer formation. Furthermore, retrospective studies analyzing response to tamoxifen therapy in a subset of patients with ER-positive breast cancer expressing either wild-type or mutant p53 suggest that the presence of wild-type p53 is an important determinant of positive therapeutic response. Source


Kalle A.M.,University of Hyderabad | Sachchidanand S.,Lupin Research Park | Pallu R.,University of Hyderabad
Leukemia Research | Year: 2010

Our previous studies have shown that overexpression of MDR1 and cyclooygenase-2 (COX-2) resulted in resistance development to imatinib in chronic myelogenous leukemia (CML) K562 (IR-K562) cells. In the present study, the regulatory mechanism of MDR1 induction by COX-2 was investigated. A gradual overexpression of MDR1 and COX-2 during the process of development was observed. Furthermore, down regulation of MDR1 upon COX-2 knockdown by siRNA showed a decrease in the PKC levels and activation of PKC by addition of PGE2 to K562 cells, suggesting a role for PKC in the COX-2 mediated induction of MDR1. The present study demonstrates COX-2 induction by HDACs and MDR1 induction by COX-2 via PGE2-cAMP-PKC-mediated pathway. © 2010 Elsevier Ltd. Source


Shiradkarb M.R.,Lupin Research Park | Botharac K.G.,Sinhgad Institute of Pharmacy
Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry | Year: 2011

The reaction of ethyl 2-amino-4-methylthiazole-5-carboxylate 1 with acetic anhydride followed by reaction with hydrazine hydrate yields the ethyl 2-acetamido-4-methylthiazole-5- carboxylate 2 and N-[5-(hydrazinecarbonyl)-4- methylthiazol-2- yl]acetamide 3, respectively. The compound 3 on further reaction with alcoholic potassium hydroxide-carbon disulphide followed by cyclization with hydrazine hydrate gives N-[5-(4-amino-5- mercapto-4H-1,2,4- triazol-3-yl)-4-methylthiazol-2-yl]acetamide 5. The compound 5 is then condensed with different aromatic aldehydes to offer Schiff bases 6a-h. The Schiff bases on cyclization with chloroacetyl chloride in presence of triethylamine as catalyst furnish the azetidin-2-one 7a-h. The compounds are synthesized in good yield and the chemical structures of the compounds are elucidated from their IR, 1H NMR, and elemental analysis. All the synthesized compounds have been screened for their antimicrobial activity. Source


Dhalwal K.,Bharati Vidyapeeth Deemed University | Shinde V.M.,Bharati Vidyapeeth Deemed University | Singh B.,Lupin Research Park | Mahadik K.R.,Bharati Vidyapeeth Deemed University
International Journal of Phytomedicine | Year: 2010

In the present study, the anti-diabetic effect of aqueous extract of Sida rhombifolia ssp. retusa (Malvaceae) leaves was studied in normal and streptozotocin (STZ)-induced (60 mg/kg, single intraperitoneal injection) diabetic rats. Hypoglycemic activity in normal rats was tested after administration of 200 mg/kg of extract. Aqueous extract showed a 15% reduction in plasma glucose level after 1.5 h of extract administration. When tested in STZ-induced diabetic rats the reduction in plasma glucose was 17%. In oral glucose tolerance test in normal rats and STZ-induced rats the decrease in AUC was 15 and 7% respectively. Glibenclamide was used as reference drug and showed significant hypoglycemic effects in normal rats but had marginal activity in STZ-induced diabetic rats. In hypolipidemic study a dose of 200 mg/kg of aqueous extract has shown reduction in triglycerides (TG) (16%), cholesterol (4%), and glucose level (10%). Fenofibrate was used as standard drug for hypolipidemic study. The results obtained from the experiment provided scientific evidence in favor of the traditional use of Sida rhombifolia ssp. retusa leaves for the treatment of diabetes mellitus. © arjournals.org, All rights reserved. Source

Discover hidden collaborations