Molekularbiologie: Open Access

Traditional plants have been a great source of medicine in developing countries, such as African countries, India and China. But in the 20^th century, scientists in both developed and developing countries have been growing interest in medicinal plants due to their observed antibacterial and anti-proliferative properties. Accordingly, the study was aimed to investigate possible anti-proliferative effects of K. foetidissima that are associated with the potential anticarcinogenic properties in breast cancer. MCF-7 and YMB-1 cell lines were exposed to different concentrations (0-100 μg/ml) of the crude methanolic extract to evaluate their growth inhibitory and apoptosis inducing effects. The extract elicited a dose- and time-dependent inhibition of cell proliferation, followed by a concomitant decrease in cell viability. The observed cytotoxicity was linked to the induction of apoptosis as determined by biochemical features known to be associated with the advent of apoptosis. Real time quantitative RT-PCR of p53 and Retinoblastoma Binding Protein 6 (RBBP6) exhibited aberrant expression profiles of these genes under various treatment conditions. Taken together, the data suggest that the crude methanolic extracts contains bioactive compounds that may be beneficial in the treatment of breast cancer, and that this apparent antineoplastic activity is a consequence of anti-proliferation rather than a particular molecular mechanism associated with the above genes.

Based on analysis of biological processes in the same low expression Parathyroid Hormone-Like Hormone (PTHLH) activated feedback mitosis and downstream DNA replication-mediated cell proliferation Gene Ontology (GO) network of no-tumor Hepatitis/Cirrhotic Tissues (HBV or HCV infection) compared with the corresponding high expression (fold change ≥2) activated (Gene Ontology) GO network of human Hepatocellular Carcinoma (HCC), we proposed PTHLH activated network that upstream consisted of cell division, cell proliferation, mitosis, mitotic checkpoint, nucleosome assembly, spindle organization and biogenesis; Downstream network cell cycle, cell cycle arrest, centrosome cycle, chromosome segregation, DNA replication, DNA replication checkpoint, G1/S transition of mitotic cell cycle, mitotic chromosome condensation, mitotic G2 checkpoint, mitotic spindle checkpoint, positive regulation of cell proliferation, regulation of cell proliferation, traversing start control point of mitotic cell cycle, positive regulation of DNA repair, postreplication repair, DNA damage response, response to DNA damage stimulus, cell division, cell proliferation, mitosis, mitotic checkpoint, nucleosome assembly, spindle organization and biogenesis, as a result of feedback mitosis to downstream DNA replication coupling postreplication repair-induced cell proliferation in no-tumor hepatitis/cirrhotic tissues. Our hypothesis was verified by the different PTHLH activated feedback mitosis and downstream DNA replication-mediated cell proliferation GO network of no-tumor hepatitis/cirrhotic tissues compared with the corresponding inhibited GO network of HCC, or the same compared with the corresponding inhibited GO network of no-tumor hepatitis/cirrhotic tissues. We constructed PTHLH feedback mitosis to downstream DNA replication coupling postreplication repair-induced cell proliferation network that upstream BUB1B activated PTHLH, and downstream PTHLH-activated BUB1B, CCNA2, CDC6, BRCA1 in no-tumor hepatitis/cirrhotic tissues from (Gene Expression Omnibus) GEO data set using gene regulatory network inference method and our programming.

We constructed the significant high expression (fold change ≥ 2) cytosolic iron-sulfur protein assembly 1 (CIAO1) downstream activation of phospholipase A2 and hormone-mediated signaling-induced cell death network in human Hepato Cellular Carcinoma (HCC), compared with low expression no-tumor hepatitis/cirrhotic tissues (HBV or HCV infection) in GEO data set, by using integration of gene regulatory activated and inhibited network inference method. Our result showed that CIAO1 downstream activation of phospholipase A2 and hormone-mediated signaling-induced cell death upstream network had no result, and downstream CIAO1-activated PLA2G1B, NUP62 in HCC. By integrative analysis of biological processes simultaneous occurrence between the different CIAO1 activated downstream cell death gene ontology (GO) network of HCC compared with CIAO1 activated downstream cell death GO network of no-tumor hepatitis/cirrhotic tissues, and the same compared CIAO1 inhibited downstream cell death GO network of no-tumor hepatitis/cirrhotic tissues, or the different compared CIAO1 inhibited downstream cell death GO network of HCC, we proposed and verified that CIAO1 activated upstream network had no result; Downstream network consisted of activation of phospholipase A2, cell death, protein kinase cascade, regulation of signal transduction, hormonemediated signaling, negative regulation of epidermal growth factor receptor signaling pathway, negative regulation of MAPK (Mitogen Activated Protein Kinase) activity, negative regulation of Ras protein signal transduction in HCC, as a result of downstream activation of phospholipase A2 and hormone-mediated signaling-induced cell death in HCC.