ABSTRACT
Genistein is one of the major isoflavones in soy products. It has been reported that genistein has apoptotic effects on certain hematological malignancies. However, so far there have been no completely comparative studies of the effect of genistein on malignant hematological diseases, especially multiple myeloma. We investigated genistein's inhibitory effect on the growth of acute lymphoblastic leukemia (RS4;11 and CEM), lymphoma (Toledo and GA10) and multiple myeloma (OPM-2 and U266) cell lines in vitro. We observed that genistein dose- and time-dependently inhibited proliferation of these cells. The cell line sensitivity to genistein treatment based on the 50% inhibitory concentration (IC(50)) values in decreasing order of toxicity was found to be as follows: RS4;11 (4.89 ± 4.28 µM) > GA10 (13.08 ± 3.49 µM) > Toledo (16.94 ± 3.89 µM) > CEM (17.31 ± 0.72 µM) > OPM-2 (46.76 ± 2.26 µM) > U266 (128.82 ± 1.90 µM). The mechanism of growth inhibition was through induction of apoptosis and cell cycle arrest. The concomitant altered expression of apoptosis pathway proteins and cell cycle modulators (caspases 9, 3, 7, PARP [poly(ADP-ribose) polymerase], cIAP1 [inhibitor of apoptosis protein 1], Bcl-2 and cyclin B1) were observed by Western blot and real-time polymerase chain reaction (PCR) analyses. In addition, some malignancy-related embryologic pathway proteins, e.g. Notch1 and Gli1, were modulated by genistein treatment in sensitive cell lines.
Subject(s)
Antineoplastic Agents/pharmacology , Apoptosis/drug effects , Genistein/pharmacology , Lymphoma/metabolism , Multiple Myeloma/metabolism , Precursor Cell Lymphoblastic Leukemia-Lymphoma/metabolism , Apoptosis Regulatory Proteins/genetics , Apoptosis Regulatory Proteins/metabolism , Cell Cycle/drug effects , Cell Line, Tumor , Cell Proliferation/drug effects , Humans , Lymphoma/genetics , Multiple Myeloma/genetics , Precursor Cell Lymphoblastic Leukemia-Lymphoma/geneticsABSTRACT
The objective of this research is to evaluate the usefulness of a macroscopic, fluorescent, imaging technique to quantify spatiotemporal mass transport parameters in in vitro solid tumor tissues taken from rat models. Fluorescent images captured during the experiments are digitally analyzed to determine the concentration of a fluorescent marker dye as it diffuses into tissue specimens taken from rat tumors. The collected concentration data are used to estimate local diffusion coefficients. An analysis of the distribution of the local diffusion data indicates that the local diffusion coefficient is spatially dependent within the tumor tissue. When mass transfer is restricted to one dimension, the current technique can be used to determine the concentration distribution of fluorescent molecules on the tissue surface and to estimate the mass transfer parameters within the heterogeneous tumor tissue.