ABSTRACT
The cytotoxic activity of Stachys plants and of aucubin and harpagide against MCF7-breast adenocarcinoma, HeLa-cervix adenocarcinoma, A431-skin carcinoma of epithelial origin is reported in this study. Cisplatin and doxorubicin were use as reference compound.
Subject(s)
Antineoplastic Agents, Phytogenic/pharmacology , Cytotoxins/pharmacology , Neoplasms/drug therapy , Phytotherapy , Plant Extracts/therapeutic use , Stachys , Cell Line, Tumor , Cell Proliferation/drug effects , Female , Glucosides/isolation & purification , Glucosides/pharmacology , Glucosides/therapeutic use , Humans , Iridoid Glucosides , Iridoid Glycosides , Iridoids/isolation & purification , Iridoids/pharmacology , Iridoids/therapeutic use , Plant Components, Aerial , Plant Extracts/isolation & purification , Plant Extracts/pharmacology , Pyrans/isolation & purification , Pyrans/pharmacology , Pyrans/therapeutic useABSTRACT
A previously developed experimental system was applied to obtain qualitative and quantitative data on the contribution of TCR-, CD4- and CD28-mediated signalling in the activation of an antigen specific T-cell hybridoma. All the three signal transducing receptors were stimulated by their natural ligands, and intermediate and late responses of an I-Ed restricted, CD4 +, influenza HA specific murine T-hybridoma (IP-12-7) were monitored by measuring the concentration of intracellular calcium [Ca2+]i and secreted IL-2. This type of analysis of T-cell activation revealed: (i) calcium mobilization induced by peptide loaded APC requires rapid conjugate formation; (ii) a direct correlation between the magnitude of the intermediate and the late responses was observed as a consequence of differential TCR ligation modulated by peptide dose or by the presence CD4; (iii) considering the APC/peptide and T/APC ratios, the concentration dependence of the intermediate and late responses was similar in both assays but a substantial difference in the sensitivity of the two methods was observed; (iv) CD4 mediated signalling has a co-stimulatory effect predominantly at suboptimal in vitro conditions; and (v) sustained increase of [Ca2+]i as well as the production of high concentrations of IL-2 is highly dependent on the CD28-B7 interaction. These results demonstrate that distinct peptide doses and the presence or absence of CD4 result in quantitative changes in T-cell responses, while the degree of CD28 mediated signalling has a qualitative affect on the outcome of T-cell activation, revealed by complete or partial inhibition of IL-2 secretion as a result of limited CD28-B7 interaction as well as by alteration in the duration and time kinetics of the calcium response.
