Delineating the Antiapoptotic Property of Apigenin as an Antitumor Agent: A Computational and In Vitro Study on HeLa Cells.

Apigenin, a flavonoid, is reported to have multiple health benefits including cancer prevention; this study evaluates the drug likeliness and Swiss ADME properties of apigenin. Apoptosis, which is a key hallmark of cancer, is associated with the deregulation of the balance between proapoptotic proteins and antiapoptotic proteins such as BCL-2,BCL-xl, BFL-1, BCL-w, BRAG-16, and MCL-1. The docking studies of apigenin with the mentioned proteins was performed to identify the interactions between the ligand and proteins, which suggested that apigenin was able to bind to most of the proteins similar to the inhibitory molecules of its native structure. A remarkable reduction in the total energy after energy minimization of apigenin-antiapoptotic protein complexes suggested increased stability of the docked complexes. The same complexes were found to be stable over a 10 ns period of molecular simulation at 300 K. These findings advocated the study to evaluate apigenin's potential to inhibit the HeLa cells at 5, 10, and 15 µM concentrations in the clonogenic assay. Apigenin inhibited the colony-forming ability of HeLa cells in a dose-dependent manner over a fortnight. Light microscopy of the treated cells displayed the morphological evidence characteristic of apoptosis in HeLa cells such as blebbing, spike formation, cytoplasmic oozing, and nuclear fragmentation. Thus, these results clearly indicate that apigenin may be used as a potential chemopreventive agent in cervical cancer management.

An in silico analytical study of lung cancer and smokers datasets from gene expression omnibus (GEO) for prediction of differentially expressed genes.

Smoking is the leading cause of lung cancer development and several genes have been identified as potential biomarker for lungs cancer. Contributing to the present scientific knowledge of biomarkers for lung cancer two different data sets, i.e. GDS3257 and GDS3054 were downloaded from NCBI׳s GEO database and normalized by RMA and GRMA packages (Bioconductor). Diffrentially expressed genes were extracted by using and were R (3.1.2); DAVID online tool was used for gene annotation and GENE MANIA tool was used for construction of gene regulatory network. Nine smoking independent gene were found whereas average expressions of those genes were almost similar in both the datasets. Five genes among them were found to be associated with cancer subtypes. Thirty smoking specific genes were identified; among those genes eight were associated with cancer sub types. GPR110, IL1RN and HSP90AA1 were found directly associated with lung cancer. SEMA6A differentially expresses in only non-smoking lung cancer samples. FLG is differentially expressed smoking specific gene and is related to onset of various cancer subtypes. Functional annotation and network analysis revealed that FLG participates in various epidermal tissue developmental processes and is co-expressed with other genes. Lung tissues are epidermal tissues and thus it suggests that alteration in FLG may cause lung cancer. We conclude that smoking alters expression of several genes and associated biological pathways during development of lung cancers.

Lack of association of BRCA1 and BRCA2 variants with breast cancer in an ethnic population of Saudi Arabia, an emerging high-risk area.

Incidence of breast cancer shows geographical variation, even within areas of ethnic homogeneity. Saudi Arabia has witnessed an increase in occurrence of breast cancer in its unexplored ethnic populations over the past few years. We aimed at determining whether any association exists between single nucleotide polymorphisms in breast cancer associated gene 1 (BRCA1) and breast cancer associated gene 2 (BRCA2) and the risk of breast cancer. TaqMan based Real Time Polymerase chain reaction genotyping assays were used to determine the frequency of single nucleotide polymorphisms in BRCA1 (rs799917) and BRCA2 (rs144848) in a group of 100 breast cancer patients and unaffected age matched controls of Saudi Arabian origin. The present data revealed that neither BRCA1 nor the BRCA2 studied variant show any significant association with the disease. This study failed to find any role of the concerned variants in breast cancer either as risk or as prognostic factors. The small number of patients registered was one of the limitations of this study. In summary, comparison of mutation profile with other ethnic populations and regions reflected both differences and similarities indicating co-exposure to a unique set of risk factors. The differences could be due to exposure to particular environmental carcinogens; different lifestyle, reproductive pattern; dietary or cultural practices of Saudi Arabian women that need further investigations.

Fenugreek induced apoptosis in breast cancer MCF-7 cells mediated independently by fas receptor change.

Trigonella foenum in graecum (Fenugreek) is a traditional herbal plant used to treat disorders like diabetes, high cholesterol, wounds, inflammation, gastrointestinal ailments, and it is believed to have anti-tumor properties, although the mechanisms for the activity remain to be elucidated. In this study, we prepared a methanol extract from Fenugreek whole plants and investigated the mechanism involved in its growth-inhibitory effect on MCF- 7 human breast cancer cells. Apoptosis of MCF-7 cells was evidenced by investigating trypan blue exclusion, TUNEL and Caspase 3, 8, 9, p53, FADD, Bax and Bak by real-time PCR assays inducing activities, in the presence of FME at 65 µg/mL for 24 and 48 hours. FME induced apoptosis was mediated by the death receptor pathway as demonstrated by the increased level of Fas receptor expression after FME treatment. However, such change was found to be absent in Caspase 3, 8, 9, p53, FADD, Bax and Bak, which was confirmed by a time-dependent and dose-dependent manner. In summary, these data demonstrate that at least 90% of FME induced apoptosis in breast cell is mediated by Fas receptor-independently of either FADD, Caspase 8 or 3, as well as p53 interdependently.

Predicting the possibility of two newly isolated phenetheren ring containing compounds from Aristolochia manshuriensis as CDK2 inhibitors.

UNLABELLED: 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. ABBREVIATIONS: CDK2 - cyclin-dependent kinase 2, OLO - Olomoucine, NW1 - Cyclohexylmethyloxy-5-Nitroso-Pyrimidine- 2, 4-Diamine, CMG - 6-O-Cyclohexylmethyl Guanine.