ABSTRACT
Two new lignans, pseuderesinol (1), pseuderanoside (2) and a new triterpene, pseuderanic acid (3) were isolated from the dried root of Pseuderanthemum carruthersii (SEEM.) GUILL. var. atropurpureum (BULL.) FOSB. (Acanthaceae), together with ten known compounds, including five lignans, (+)-eudesmin (4), (+)-magnolin (5), (+)-syringaresinol (6), (+)-episyringaresinol (7), (+)-1-hydroxysyringaresinol (8) and five triterpenes, squalene (9), oleanolic acid (10), lupeol (11), betulin (12), betulinic acid (13). Their chemical structures were elucidated by 1D- and 2D-NMR, computational quantum chemistry, as well as high resolution-electrospray ionization (HR-ESI)-MS spectroscopic analysis. The acetylcholinesterase inhibition and cytotoxic activities against HeLa and MCF-7 cancer cell lines were evaluated on some purified compounds at the concentration of 100 µg/mL. Pseuderesinol (1) and magnolin (5) exhibited moderate cytotoxic activities against the MCF-7 cancer cell line.
Subject(s)
Acanthaceae/chemistry , Antineoplastic Agents, Phytogenic/pharmacology , Lignans/pharmacology , Plant Roots/chemistry , Triterpenes/pharmacology , Antineoplastic Agents, Phytogenic/chemistry , Antineoplastic Agents, Phytogenic/isolation & purification , Cell Line, Tumor , Cell Survival/drug effects , Humans , Lignans/chemistry , Lignans/isolation & purification , Neoplasms/drug therapy , Triterpenes/chemistry , Triterpenes/isolation & purificationABSTRACT
Previous studies have shown that a field of genetically altered but histologically normal tissue extends 1 cm or more from the margins of human breast tumors. The extent, composition and biological significance of this field are only partially understood, but the molecular alterations in affected cells could provide mechanisms for limitless replicative capacity, genomic instability and a microenvironment that supports tumor initiation and progression. We demonstrate by microarray, qRT-PCR and immunohistochemistry a signature of differential gene expression that discriminates between patient-matched, tumor-adjacent histologically normal breast tissues located 1 cm and 5 cm from the margins of breast adenocarcinomas (TAHN-1 and TAHN-5, respectively). The signature includes genes involved in extracellular matrix remodeling, wound healing, fibrosis and epithelial to mesenchymal transition (EMT). Myofibroblasts, which are mediators of wound healing and fibrosis, and intra-lobular fibroblasts expressing MMP2, SPARC, TGF-ß3, which are inducers of EMT, were both prevalent in TAHN-1 tissues, sparse in TAHN-5 tissues, and absent in normal tissues from reduction mammoplasty. Accordingly, EMT markers S100A4 and vimentin were elevated in both luminal and myoepithelial cells, and EMT markers α-smooth muscle actin and SNAIL were elevated in luminal epithelial cells of TAHN-1 tissues. These results identify cellular processes that are differentially activated between TAHN-1 and TAHN-5 breast tissues, implicate myofibroblasts as likely mediators of these processes, provide evidence that EMT is occurring in histologically normal tissues within the affected field and identify candidate biomarkers to investigate whether or how field cancerization contributes to the development of primary or recurrent breast tumors.
