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author:("shaft, gowar")
1.  Differential Expression Profile and Genetic Variants of MicroRNAs Sequences in Breast Cancer Patients 
PLoS ONE  2012;7(2):e30049.
The technology available for cancer diagnosis and prognosis is not yet satisfactory at the molecular level, and requires further improvements. Micro RNAs (miRNAs) have been recently reported as useful biomarkers in diseases including cancer. We performed a miRNA expression profiling study using peripheral blood from breast cancer patients to detect and identify characteristic patterns. A total of 100 breast cancer patients and 89 healthy patients were recruited for miRNA genotyping and expression profiling. We found that hs-miR-196a2 in premenopausal patients, and hs-miR-499, hs-miR-146a and hs-miR-196a2 in postmenopausal patients, may discriminate breast cancer patients from healthy individuals. In addition, we found a significant association between two microRNA polymorphisms (hs-miR-196a2 and hs-miR-499) and breast cancer risk. However, no significant association between the hs-miR-146a gene and breast cancer risk was found. In summary, the study demonstrates that peripheral blood miRNAs and their expression and genotypic profiles can be developed as biomarkers for early diagnosis and prognosis of breast cancer.
PMCID: PMC3282723  PMID: 22363415
2.  Validation of the Antiproliferative Effects of Organic Extracts from the Green Husk of Juglans regia L. on PC-3 Human Prostate Cancer Cells by Assessment of Apoptosis-Related Genes 
With the increased use of plant-based cancer chemotherapy, exploring the antiproliferative effects of phytochemicals for anticancer drug design has gained considerable attention worldwide. This study was undertaken to investigate the effect of walnut green husk extracts on cell proliferation and to determine the possible molecular mechanism of extract-induced cell death by quantifying the expression of Bcl-2, Bax, caspases-3, and Tp53. PC-3 human prostate cancer cells. In this study, we found that green husk extracts suppressed proliferation and induced apoptosis in a dose- and time-dependent manner by modulating expression of apoptosis-related genes. This involved DNA fragmentation (determined by TUNEL assay) and significant changes in levels of mRNA and the expression of corresponding proteins. An increase in expressions of Bax, caspase-3, and tp53 genes and their corresponding proteins was detected using real-time PCR and western blot analysis in PC-3 cells treated with the green husk organic extracts. In contrast, Bcl2 expression was downregulated after exposure to the extracts. Our data suggest the presence of bioactive compound(s) in walnut green husks that are capable of killing prostate carcinoma cells by inducing apoptosis and that the husks are a candidate source of anticancer drugs.
PMCID: PMC3291301  PMID: 22454652
3.  Affinity of estrogens for human progesterone receptor A and B monomers and risk of breast cancer: a comparative molecular modeling study 
The human progesterone receptor (hPR) belongs to the steroid receptor family. It may be found as monomers (A and B) and or as a dimer (AB). hPR is regarded as the prognostic biomarker for breast cancer. In a cellular dimer system, AB is the dominant species in most cases. However, when a cell coexpresses all three isoforms of hPR, the complexity of the action of this receptor increases. For example, hPR A suppresses the activity of hPR B, and the ratio of hPR A to hPR B may determine the physiology of a breast tumor. Also, persistent exposure of hPRs to nonendogenous ligands is a common risk factor for breast cancer. Hence we aimed to study progesterone and some nonendogenous ligand interactions with hPRs and their molecular docking.
Methods and results
A pool of steroid derivatives, namely, progesterone, cholesterol, testosterone, testolectone, estradiol, estrone, norethindrone, exemestane, and norgestrel, was used for this in silico study. Dockings were performed on AutoDock 4.2. We found that estrogens, including estradiol and estrone, had a higher affinity for hPR A and B monomers in comparison with the dimer, hPR AB, and that of the endogenous progesterone ligand. hPR A had a higher affinity to all the docked ligands than hPR B.
This study suggests that the exposure of estrogens to hPR A as well as hPR B, and more particularly to hPR A alone, is a risk factor for breast cancer.
PMCID: PMC3169952  PMID: 21918635
human progesterone receptor; breast cancer; steroid derivatives; estrogens; molecular docking
4.  Predicting the possibility of two newly isolated phenetheren ring containing compounds from Aristolochia manshuriensis as CDK2 inhibitors 
Bioinformation  2011;7(7):334-338.
Aristolochia manshuriensis has been used for centuries in Chinese medicinal system for their versatile medicinal uses. Recent studies have revealed two new aristolactames (compound A and B) with γ-lactame ring fused with the phenentherene ring as potent inhibitors of human Cycline Dependent Kinase2 (CDK2). Studies on aristolactames and related compounds claim for their CDK2 inhibition without delineating the involved mechanism and structural basis of interaction. Molecular structural model was used to we propose a structural basis of CDK2 inhibition. We showed that these compounds (A and B) can successfully dock into the inhibitor binding pockets of human CDK2. Predicted binding affinities are comparable to known inhibitors of CDK2. Results were in agreement with the earlier biochemical studies. Hence, suggest that studied compounds A and B can be a promising scaffold for rational design of novel and potential drugs against cancer.
CDK2 - cyclin-dependent kinase 2, OLO - Olomoucine, NW1 - Cyclohexylmethyloxy-5-Nitroso-Pyrimidine- 2, 4-Diamine, CMG - 6-O-Cyclohexylmethyl Guanine.
PMCID: PMC3280487  PMID: 22355233
Aristolactame; Cycline Dependent Kinase2; Docking; AutoDock; Molecular docking Server
5.  Analysis of casein alpha S1 & S2 proteins from different mammalian species 
Bioinformation  2010;4(9):430-435.
Nowadays, the quality of any food used for human consumption is, to a considerable extent, considered by its possible contribution to the maintenance or improvement of the consumer's health. In developed countries there is increasing interest in goat milk and its derivates, the quality of which is considered of special importance in the light of current tendencies favouring healthy eating. In particular, goat's milk is a hypoallergenic alternative to cow's milk in the human diet. In the present work, we studied the casein alpha S1 and S2 proteins of cow, goat and sheep for comparative analysis. We found that the amino acid sequence of these proteins is almost same in goat and sheep but there are several changes at different base pairs when these two sequences are compared with cow. Prediction of secondary structures (GOR) was performed for alpha s1 and s2 proteins to gain functional insights. Our in silico study revealed considerable identity in chemical properties between goat and sheep but a considerable dissimilarity in cow with goat and sheep casein proteins. Moreover, the effect amino acid change on secondary structures in the three species is discussed. There was no significant difference found between goat and sheep alpha S1 and S2 proteins, so naturally both will be having same properties. The study concludes that sheep milk is another convenient alternative for the cow milk allergic children.
PMCID: PMC2951635  PMID: 20975894
casein; alpha proteins; sequence analysis
6.  Induction of apoptosis in HeLa cells by chloroform fraction of seed extracts of Nigella sativa 
Cancer remains one of the most dreaded diseases causing an astonishingly high death rate, second only to cardiac arrest. The fact that conventional and newly emerging treatment procedures like chemotherapy, catalytic therapy, photodynamic therapy and radiotherapy have not succeeded in reverting the outcome of the disease to any drastic extent, has made researchers investigate alternative treatment options. The extensive repertoire of traditional medicinal knowledge systems from various parts of the world are being re-investigated for their healing properties. This study progresses in the direction of identifying component(s) from Nigella sativa with anti cancer acitivity. In the present study we investigated the efficacy of Organic extracts of Nigella sativa seed powder for its clonogenic inhibition and induction of apoptosis in HeLa cancer cell.
Methanolic, n-Hexane and chloroform extracts of Nigella sativa seedz effectively killed HeLa cells. The IC50 values of methanolic, n-hexane, and chloroform extracts of Nigella sativa were 2.28 μg/ml, 2.20 μg/ml and 0.41 ng/ml, respectively. All three extracts induced apoptosis in HeLa cells. Apoptosis was confirmed by DNA fragmentation, western blot and terminal transferase-mediated dUTP-digoxigenin-end labeling (TUNEL) assay.
Western Blot and TUNEL results suggested that Nigella sativa seed extracts regulated the expression of pro- and anti- apoptotic genes, indicating its possible development as a potential therapeutic agent for cervical cancer upon further investigation.
PMCID: PMC2794855  PMID: 19943925

Results 1-6 (6)