AIM: To investigate in vitro and in vivo treatment with histone deacetylase inhibitors NVP-LAQ824 and NVP-LBH589 in pancreatic cancer. METHODS: Cell-growth inhibition by NVP-LAQ824 and NVP-LBH589 was studied in vitro in 8 human pancreatic cancer cell lines using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. In addition, the anti-tumoral effect of NVP-LBH589 was studied in a chimeric mouse model. Anti-tumoral activity of the drugs was assessed by immunoblotting for p21(WAF-1), acH4, cell cycle analysis, TUNEL assay, and immunohistochemistry for MIB-1. RESULTS: In vitro treatment with both compounds significantly suppressed the growth of all cancer cell lines and was associated with hyperacetylation of nucleosomal histone H4, increased expression of p21(WAF-1), cell cycle arrest at G2/M-checkpoint, and increased apoptosis. In vivo, NVP-LBH589 alone significantly reduced tumor mass and potentiated the efficacy of gemcitabine. Further analysis of the tumor specimens revealed slightly increased apoptosis and no significant reduction of cell proliferation. CONCLUSION: Our findings suggest that NVP-LBH589 and NVP-LAQ824 are active against human pancreatic cancer, although the precise mechanism of in vivo drug action is not yet completely understood. Therefore, further preclinical and clinical studies for the treatment of pancreatic cancer are recommended.
AIM: To investigate in vitro and in vivo treatment with histone deacetylase inhibitors NVP-LAQ824 and NVP-LBH589 in pancreatic cancer. METHODS: Cell-growth inhibition by NVP-LAQ824 and NVP-LBH589 was studied in vitro in 8 humanpancreatic cancer cell lines using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. In addition, the anti-tumoral effect of NVP-LBH589 was studied in a chimeric mouse model. Anti-tumoral activity of the drugs was assessed by immunoblotting for p21(WAF-1), acH4, cell cycle analysis, TUNEL assay, and immunohistochemistry for MIB-1. RESULTS: In vitro treatment with both compounds significantly suppressed the growth of all cancer cell lines and was associated with hyperacetylation of nucleosomal histone H4, increased expression of p21(WAF-1), cell cycle arrest at G2/M-checkpoint, and increased apoptosis. In vivo, NVP-LBH589 alone significantly reduced tumor mass and potentiated the efficacy of gemcitabine. Further analysis of the tumor specimens revealed slightly increased apoptosis and no significant reduction of cell proliferation. CONCLUSION: Our findings suggest that NVP-LBH589 and NVP-LAQ824 are active against humanpancreatic cancer, although the precise mechanism of in vivo drug action is not yet completely understood. Therefore, further preclinical and clinical studies for the treatment of pancreatic cancer are recommended.
Authors: Margaret Tempero; William Plunkett; Veronique Ruiz Van Haperen; John Hainsworth; Howard Hochster; Renato Lenzi; James Abbruzzese Journal: J Clin Oncol Date: 2003-07-28 Impact factor: 44.544
Authors: Laurence Catley; Ellen Weisberg; Yu-Tzu Tai; Peter Atadja; Stacy Remiszewski; Teru Hideshima; Nicholas Mitsiades; Reshma Shringarpure; Richard LeBlanc; Dharminder Chauhan; Nikhil C Munshi; Robert Schlossman; Paul Richardson; James Griffin; Kenneth C Anderson Journal: Blood Date: 2003-06-19 Impact factor: 22.113
Authors: Peter Atadja; Lin Gao; Paul Kwon; Nancy Trogani; Heather Walker; Meier Hsu; Lakshmi Yeleswarapu; Nagarajan Chandramouli; Larry Perez; Richard Versace; Arthur Wu; Lidia Sambucetti; Peter Lassota; Dalia Cohen; Kenneth Bair; Alexander Wood; Stacy Remiszewski Journal: Cancer Res Date: 2004-01-15 Impact factor: 12.701
Authors: Christiane J Bruns; Gudrun E Koehl; Markus Guba; Maksim Yezhelyev; Markus Steinbauer; Hendrik Seeliger; Astrid Schwend; Anna Hoehn; Karl-Walter Jauch; Edward K Geissler Journal: Clin Cancer Res Date: 2004-03-15 Impact factor: 12.531
Authors: Stacy W Remiszewski; Lidia C Sambucetti; Kenneth W Bair; John Bontempo; David Cesarz; Nagarajan Chandramouli; Ru Chen; Min Cheung; Susan Cornell-Kennon; Karl Dean; George Diamantidis; Dennis France; Michael A Green; Kobporn Lulu Howell; Rina Kashi; Paul Kwon; Peter Lassota; Mary S Martin; Yin Mou; Lawrence B Perez; Sushil Sharma; Troy Smith; Eric Sorensen; Francis Taplin; Nancy Trogani; Richard Versace; Heather Walker; Susan Weltchek-Engler; Alexander Wood; Arthur Wu; Peter Atadja Journal: J Med Chem Date: 2003-10-09 Impact factor: 7.446
Authors: M Cecilia Crisanti; Africa F Wallace; Veena Kapoor; Fabian Vandermeers; Melissa L Dowling; Luana P Pereira; Kara Coleman; Barbara G Campling; Zvi G Fridlender; Gary D Kao; Steven M Albelda Journal: Mol Cancer Ther Date: 2009-08-11 Impact factor: 6.261
Authors: Dmitriy I Dovzhanskiy; Stefanie M Arnold; Thilo Hackert; Ina Oehme; Olaf Witt; Klaus Felix; Nathalia Giese; Jens Werner Journal: BMC Cancer Date: 2012-06-08 Impact factor: 4.430
Authors: Günter Schneider; Oliver H Krämer; Petra Fritsche; Susanne Schüler; Roland M Schmid; Dieter Saur Journal: J Cell Mol Med Date: 2009-11-19 Impact factor: 5.310