Methodology of predicting novel key regulators in ovarian cancer network: a network theoretical approach
BMC CANCER
Authors: Malik, Md Zubbair; Chirom, Keilash; Ali, Shahnawaz; Ishrat, Romana; Somvanshi, Pallavi; Singh, R. K. Brojen
Abstract
Background Identification of key regulator/s in ovarian cancer (OC) network is important for potential drug target and prevention from this cancer. This study proposes a method to identify the key regulators of this network and their importance. Methods The protein-protein interaction (PPI) network of ovarian cancer (OC) is constructed from curated 6 hundred genes from standard six important ovarian cancer databases (some of the genes are experimentally verified). We proposed a method to identify key regulators (KRs) from the complex ovarian cancer network based on the tracing of backbone hubs, which participate at all levels of organization, characterized by Newmann-Grivan community finding method. Knockout experiment, constant Potts model and survival analysis are done to characterize the importance of the key regulators in regulating the network. Results The PPI network of ovarian cancer is found to obey hierarchical scale free features organized by topology of heterogeneous modules coordinated by diverse leading hubs. The network and modular structures are devised by fractal rules with the absence of centrality-lethality rule, to enhance the efficiency of signal processing in the network and constituting loosely connected modules. Within the framework of network theory, we device a method to identify few key regulators (KRs) from a huge number of leading hubs, that are deeply rooted in the network, serve as backbones of it and key regulators from grassroots level to complete network structure. Using this method we could able to identify five key regulators, namely, AKT1, KRAS, EPCAM, CD44 and MCAM, out of which AKT1 plays central role in two ways, first it serves as main regulator of ovarian cancer network and second serves as key cross-talk agent of other key regulators, but exhibits disassortive property. The regulating capability of AKT1 is found to be highest and that of MCAM is lowest. Conclusions The popularities of these key hubs change in an unpredictable way at different levels of organization and absence of these hubs cause massive amount of wiring energy/rewiring energy that propagate over all the network. The network compactness is found to increase as one goes from top level to bottom level of the network organization.
Artemisia annua Extract Ameliorates DMBA-induced Breast Cancer in Albino rats; Antioxidant and Genetic Effects
ORIENTAL JOURNAL OF CHEMISTRY
Authors: Faheem, Hemmat M. M.; El Nabtity, Sameh M. M.
Abstract
Breast cancer is considered a major health problem causing death in women around the world and is ranked second most common carcinoma. Millions of women are diagnosed with breast cancer every year, and more than half million women die annually due to this disease. So this work was designed to detect the effect of Artemisia annua extract as one of the famous medicinal plants on breast cancer. This study examined the anti-oxidant effects of Artemisia annua extract together with its effect on levels of tumour markers as CA 15.3 and carcino-embryonic antigen. Effects of Artemisia annua extract on mRNA expression of Bax, AKT1, CYP1A1 and ERBB2 were detected. Our results showed significant decline of levels of total antioxidant capacity, SOD, CAT, GSH and GPX levels in DMBA administered rats with significant elevation in Artemisia annua extract treated groups(P<0.05). Significant increase of MDA level in DMBA administered rats was detected with significant decline in Artemisia annua extract treated groups (P<0.05). Significant up-regulation of mRNA expressions of AKT1, CYP1A1 and ERBB2 were detected in DMBA administered rats with significant normalization in Artemisia annua extract treated groups (P<0.05). Finally, we recommend use of Artemisia annua extract as a promising complementary drug in case of breast cancer.