Growth and differentiation, cellular

Shermilamines B (37) and C (38) (and also diplamine 46) showed dose-dependent inhibition of proliferation in HCT cells in vitro and inhibited the topoisomerase (TOPO) II-mediated decatenation of kinetoplast DNA (kDNA) in a dose-dependent manner [41]. These results suggest a possible cytotoxicity mechanism for these compounds. Furthermore, shermilamine B also displayed cytotoxicity against KB cells [43] and was reported as a potent regulator of cellular growth and differentiation, affecting cAMP-mediated processes [44]. 

Several isoforms of tyrosine protein kinase play roles in cellular growth and differentiation. The assay of Boutin et al. (1992), exploits the use of hydrophilic interaction chromatography to separate hydrophilic peptides. 

The polyamines were chosen since the native compounds, putrescine, spermidine and spermine, bind electrostatically to DNA, are essential both for cellular growth and differentiation, and their depletion inhibits the growth of tumors. Representative compounds that were initially synthesized are the o-carboranyl substituted analogs, SPD-5 and SPM-1, shown below ... 

The MCF-7 cell line is a human breast cancer cell line with differentiation potential [8, 9] that provides a system to study in vitro the interaction of the process of ADP-ribosylation with reagents that may modify the adenylate cyclase system and a system to study the effect of hormonal manipulation of cellular growth and differentiation on these same processes. 

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