TY  - JOUR
AU  - Adwan, Hassan
AU  - Murtaja, Ahmed
AU  - Kadhim Al-Taee, Khamael
AU  - Pervaiz, Asim
AU  - Hielscher, Thomas
AU  - Berger, Martin
TI  - Riproximin's activity depends on gene expression and sensitizes PDAC cells to TRAIL.G401
JO  - Cancer biology & therapy
VL  - 15
IS  - 9
SN  - 1555-8576
CY  - Georgetown, Tex.
PB  - Landes Bioscience
M1  - DKFZ-2017-00155
SP  - 1185 - 1197
PY  - 2014
AB  - Riproximin (Rpx) is a type II ribosome inactivating protein, which was investigated for its activity in pancreatic ductal adenocarcinoma (PDAC) in a panel of 17 human and rat PDAC cell lines and in rat pancreatic cancer liver metastasis. Cytotoxicity in response to Rpx was determined by MTT assay, apoptosis by flow cytometry and qRT-PCR for apoptosis related genes, and the modulation of the transcriptome was monitored by micro array analysis. The combination effect of Rpx and TRAIL was assessed by MTT assay. Rpx showed high but varying cytotoxicity in PDAC cells. Based on overall gene expression, the sensitivity of these cells was linked to genes involved in apoptosis. Furthermore, based on the affinity of Rpx for CEA, the expression of carcinoembryonic antigen-related cell adhesion molecule (CEACAM) genes was significantly related to Rpx's cytotoxicity in cells with CEACAM gene expression. Exposure of Suit2-007 cells to Rpx induced the mRNA expression of members of signaling pathways initiating from most death receptors, and down modulation of TRAIL. Apoptosis was increased as shown by FACS analysis. Combination of Rpx with TRAIL resulted in a synergistic cytotoxic effect in human Suit2-007 and rat ASML cells, as evidenced by a 6-fold lower tumor cell survival than expected from an additive combination effect. Treatment of BDX rats bearing intra-portally implanted Suit2-007 cells showed a highly significant anticancer effect and indicated an application of Rpx against pancreatic cancer metastasis to the liver. These data favor further evaluation of Rpx as anticancer agent in PDAC.
KW  - Antineoplastic Agents (NLM Chemicals)
KW  - Apoptosis Regulatory Proteins (NLM Chemicals)
KW  - Plant Proteins (NLM Chemicals)
KW  - TNF-Related Apoptosis-Inducing Ligand (NLM Chemicals)
KW  - riproximin protein, Ximenia americana (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:24918923
C2  - pmc:PMC4128861
DO  - DOI:10.4161/cbt.29503
UR  - https://inrepo02.dkfz.de/record/119413
ER  -