Abstract | UNLABELLED: PURPOSE: To determine whether CARP-1 is a novel suppressor of lymphoma growth. METHODS: Flow cytometric analyses coupled with Western immunoblotting, cell growth, apoptosis, and immunocytochemistry methodologies were utilized to determine CARP-1-dependent lymphoma growth inhibition in vitro and in vivo. RESULTS: CARP-1 expression correlated with activated caspase-3 and inversely correlated with activated Akt in DLCL. Exposure to adriamycin stimulated CARP-1 expression and inhibited growth of Raji cells, but not CHOP-resistant WSU-DLCL2 cells. Expression of wild-type CARP-1 or its apoptosis-inducing mutants inhibited growth of Raji as well as CHOP-resistant WSU-DLCL2 cells, in part by activating caspase-9 and apoptosis. Since CARP-1 harbors multiple, apoptosis-promoting subdomains, we investigated whether epigenetic compensation of CARP-1 function by intracellular delivery of trans-activator of transcription (TAT) domain-tagged CARP-1 peptide(s) will inhibit lymphoma growth. Treatments with TAT-tagged CARP-1 peptides suppressed growth of the Raji and WSU-DLCL2 cells by stimulating apoptosis. TAT-CARP-1 (1-198) as well as (896-1150) peptides also suppressed growth of WSU-DLCL2 cell-derived tumor xenografts in SCID mice, while administration of TAT-CARP-1 (1-198) also inhibited growth of WSU-FSCCL cell-derived ascites and prolonged host survival. CONCLUSION: CARP-1 is a suppressor of NHL growth and could be exploited for targeting the resistant DLCL.
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Authors | Edi Levi, Liyue Zhang, Amro Aboukameel, Sunny Rishi, Ramzi M Mohammad, Lisa Polin, James S Hatfield, Arun K Rishi |
Journal | Cancer chemotherapy and pharmacology
(Cancer Chemother Pharmacol)
Vol. 67
Issue 6
Pg. 1401-13
(Jun 2011)
ISSN: 1432-0843 [Electronic] Germany |
PMID | 20809119
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)
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Chemical References |
- Antibiotics, Antineoplastic
- Apoptosis Regulatory Proteins
- CCAR1 protein, human
- Carrier Proteins
- Cell Cycle Proteins
- Peptide Fragments
- Doxorubicin
- Proto-Oncogene Proteins c-akt
- Caspase 3
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Topics |
- Animals
- Antibiotics, Antineoplastic
(pharmacology)
- Apoptosis
- Apoptosis Regulatory Proteins
- Carrier Proteins
(biosynthesis, genetics, physiology)
- Caspase 3
(metabolism)
- Cell Cycle Proteins
- Cell Line, Tumor
- Cell Proliferation
- Doxorubicin
(pharmacology)
- Humans
- Lymphoma, Large B-Cell, Diffuse
(metabolism, pathology)
- Mice
- Mice, SCID
- Mutation
- NIH 3T3 Cells
- Neoplasm Transplantation
- Peptide Fragments
(pharmacology)
- Proto-Oncogene Proteins c-akt
(metabolism)
- Transplantation, Heterologous
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