An Overview to the Structure and Function of Nuclear Matrix

Although the genome is defined by its primary sequence, its functional properties, aredetermined by far more complex mechanisms and depend on multiple layers of nuclearorganization. The architecture of the nucleus includes two overlapping structures: the chromatinand a framework structure named the nuclear matrix. Ultra-structural studies revealthat the nuclear matrix is a network consisting of branched core filaments masked with alarge number of hnRNPs and regulatory proteins. This scaffold has been demonstrated tobe an active and dynamic structure, anchoring the nuclear processes such as replication,transcription and splicing making nuclear domains/foci. It is postulated that the nuclearmatrix serves as a dynamic support to bring together specific DNA sequences with factorsinvolved in the regulation of genome functions. In this review, we attempt to introduce thestructure and function of nuclear matrix as an active intra-nuclear factor, having a criticaldynamic role to organize different nuclear functions. Studying in vivo variations of this epigeneticparameter has been suggested to all investigators interested in the field of chromatinstructure and itsdynamics

Synergy of theophylline reduces necrotic effect of berberine, induces cell cycle arrest and PARP, HMGB1, Bcl-2 family mediated apoptosis in MDA-MB-231 breast cancer cells

Berberine, is a plant alkaloid, proved to have anticancer effect on various cancers. Theophylline (TH), a natural product, is widely used in the treatment of respiratory difficulties. The present study designed to elucidate the effects of theophylline and berberine combination on breast cancer cells cytotoxicity, gene expression and cell cycle. MTT assay revealed that berberine inhibited MDA-MB-231 breast cancer cells viability in a time and dose dependent manner (IC50 of 100 μM) but theophylline had no considerably effect on the cells. Combined treatment of berberine and theophylline showed a synergistic anti-proliferation effect, IC50 of berberine reduced to 50 μM and the cells were arrested at G2/M phase. Combined treatment of Berberine and theophylline reduced extracellular level of HMGB1 and down regulated HMGB1 and MMP-9 mRNA expression. The results of flow cytometry using annexin/PI staining of the cells, HMGB1 release, and poly ADP ribose polymerase cleavage demonstrated that theophylline attenuated necrotic effect of berberine and increased the level of apoptotic cell death. Enhancement of Bax content detected by ELISA and upregulation of Bax mRNA expression, down-regulation of Bcl-2 expression and increase of anion superoxide production confirmed induction of apoptosis via intrinsic apoptotic pathway. Replacement of theophylline with exogenous cyclic AMP in combination treatment represented similar effect on berberine cytotoxicity. From the results it is concluded that synergistic anticancer effect of theophylline and berberine suggests that combination of these two drugs may be an effective therapeutic agent against breast cancer cell. © 2018 Elsevier Masson SA