Yuki Okuhashi1, Nobuo Nara, Shuji Tohda. 1. Department of Laboratory Medicine, Tokyo Medical and Dental University, Yushima 1-5-45, Bunkyo-Ku, Tokyo 113-8519, Japan.
Abstract
BACKGROUND: Notch activation is involved in the growth of leukemia cells. gamma-Secretase inhibitors (GSIs), which block Notch activation, may be candidates for molecular target therapy against leukemia. MATERIALS AND METHODS: The effects of three kinds of GSIs: GSI-IX, GSI-XII and GSI-XXI, on the in vitro growth of various leukemia cell lines were examined. RESULTS: The effects of GSI were diverse depending upon the combination of cells and GSI. GSI treatment suppressed the growth of most of the cell lines examined. Conversely, the growth of some cell lines were promoted by GSI-XXI. GSI-XXI treatment reduced the amount of cleaved Notch1 protein and HES1 mRNA in the cells, which means that it suppressed Notch activity. The treatment up-regulated mRNA of nuclear factor kappa-B1 (NFKB1) and v-rel reticuloendotheliosis viral oncogene homolog A (RELA), which can be a cause of growth promotion. CONCLUSION: The diverse effects of GSIs must be elucidated before clinical use because they can stimulate the growth of leukemia cells.
BACKGROUND:Notch activation is involved in the growth of leukemia cells. gamma-Secretase inhibitors (GSIs), which block Notch activation, may be candidates for molecular target therapy against leukemia. MATERIALS AND METHODS: The effects of three kinds of GSIs: GSI-IX, GSI-XII and GSI-XXI, on the in vitro growth of various leukemia cell lines were examined. RESULTS: The effects of GSI were diverse depending upon the combination of cells and GSI. GSI treatment suppressed the growth of most of the cell lines examined. Conversely, the growth of some cell lines were promoted by GSI-XXI. GSI-XXI treatment reduced the amount of cleaved Notch1 protein and HES1 mRNA in the cells, which means that it suppressed Notch activity. The treatment up-regulated mRNA of nuclear factor kappa-B1 (NFKB1) and v-rel reticuloendotheliosis viral oncogene homolog A (RELA), which can be a cause of growth promotion. CONCLUSION: The diverse effects of GSIs must be elucidated before clinical use because they can stimulate the growth of leukemia cells.
Authors: Justyna K Broniarczyk; Alicja Warowicka; Anna Kwaśniewska; Maria Wohuń-Cholewa; Wojciech Kwaśniewski; Anna Goździcka-Józefiak Journal: Oncol Lett Date: 2014-03-11 Impact factor: 2.967