PMID- 20507312 OWN - NLM STAT- MEDLINE DCOM- 20100901 LR - 20220408 IS - 1365-2141 (Electronic) IS - 0007-1048 (Print) IS - 0007-1048 (Linking) VI - 150 IP - 2 DP - 2010 Jul TI - All trans retinoic acid nanodisks enhance retinoic acid receptor mediated apoptosis and cell cycle arrest in mantle cell lymphoma. PG - 158-69 LID - 10.1111/j.1365-2141.2010.08209.x [doi] AB - Mantle cell lymphoma (MCL) is characterized by translocation t(11;14)(q13;q32), aggressive clinical behaviour, and poor patient outcomes following conventional chemotherapy. New treatment approaches are needed that target novel biological pathways. All trans retinoic acid (ATRA) is a key retinoid that acts through nuclear receptors that function as ligand-inducible transcription factors. The present study evaluated cell killing effects of ATRA-enriched nanoscale delivery particles, termed nanodisks (ND), on MCL cell lines. Results show that ATRA-ND induced cell death more effectively than naked ATRA (dimethyl sulphoxide) or empty ND. ATRA-ND induced reactive oxygen species (ROS) generation to a greater extent than naked ATRA. The antioxidant, N-acetylcysteine, inhibited ATRA-ND induced apoptosis. Compared to naked ATRA, ATRA-ND enhanced G1 growth arrest, up-regulated p21and p27, and down regulated cyclin D1. At ATRA concentrations that induced apoptosis, expression levels of retinoic acid receptor-alpha (RARalpha) and retinoid X receptor-gamma (RXRgamma) were increased. Compared to naked ATRA, ATRA-ND significantly stimulated transcriptional activity of RARA in a model carcinoma cell line. Furthermore, the RAR antagonist, Ro 41-5253, inhibited ATRA-ND induced ROS generation and prevented ATRA-ND induced cell growth arrest and apoptosis. In summary, incorporation of ATRA into ND enhanced the biological activity of this retinoid in cell culture models of MCL. FAU - Singh, Amareshwar T K AU - Singh AT AD - Division of Haematology/Oncology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA. a-singh@northwestern.edu FAU - Evens, Andrew M AU - Evens AM FAU - Anderson, Reilly J AU - Anderson RJ FAU - Beckstead, Jennifer A AU - Beckstead JA FAU - Sankar, Natesan AU - Sankar N FAU - Sassano, Antonella AU - Sassano A FAU - Bhalla, Savita AU - Bhalla S FAU - Yang, Shuo AU - Yang S FAU - Platanias, Leonidas C AU - Platanias LC FAU - Forte, Trudy M AU - Forte TM FAU - Ryan, Robert O AU - Ryan RO FAU - Gordon, Leo I AU - Gordon LI LA - eng GR - R01 CA121192/CA/NCI NIH HHS/United States GR - R37 HL064159/HL/NHLBI NIH HHS/United States GR - R43 CA141904-01/CA/NCI NIH HHS/United States GR - R01 HL064159-12/HL/NHLBI NIH HHS/United States GR - 1R43CA141904/CA/NCI NIH HHS/United States GR - P30 CA060553/CA/NCI NIH HHS/United States GR - HL-64159/HL/NHLBI NIH HHS/United States GR - R01 HL064159/HL/NHLBI NIH HHS/United States GR - R43 CA141904/CA/NCI NIH HHS/United States GR - R01 CA121192-05/CA/NCI NIH HHS/United States GR - CA121192/CA/NCI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, Non-P.H.S. DEP - 20100509 PL - England TA - Br J Haematol JT - British journal of haematology JID - 0372544 RN - 0 (Antineoplastic Agents) RN - 0 (Benzoates) RN - 0 (Cell Cycle Proteins) RN - 0 (Chromans) RN - 0 (Guanine Nucleotide Exchange Factors) RN - 0 (Neoplasm Proteins) RN - 0 (Nuclear Proteins) RN - 0 (RCC1 protein, human) RN - 0 (Reactive Oxygen Species) RN - 0 (Receptors, Retinoic Acid) RN - 0 (Retinoid X Receptors) RN - 144092-31-9 (Ro 41-5253) RN - 5688UTC01R (Tretinoin) SB - IM MH - Antineoplastic Agents/administration & dosage/*pharmacology MH - Apoptosis/drug effects MH - Benzoates/pharmacology MH - Cell Cycle/drug effects MH - Cell Cycle Proteins/biosynthesis/drug effects MH - Chromans/pharmacology MH - Drug Delivery Systems MH - Drug Evaluation, Preclinical MH - Guanine Nucleotide Exchange Factors/biosynthesis/drug effects MH - Humans MH - Lymphoma, Mantle-Cell/metabolism/*pathology MH - Nanoparticles MH - Neoplasm Proteins/biosynthesis/drug effects MH - Nuclear Proteins/biosynthesis/drug effects MH - Reactive Oxygen Species/metabolism MH - Receptors, Retinoic Acid/antagonists & inhibitors/*drug effects/metabolism MH - Retinoid X Receptors/drug effects/metabolism MH - Transcription, Genetic/drug effects MH - Tretinoin/administration & dosage/*pharmacology MH - Tumor Cells, Cultured PMC - PMC2907750 MID - NIHMS212465 COIS- Conflict-of-Interest Disclosure The authors declare no competing financial interests. EDAT- 2010/05/29 06:00 MHDA- 2010/09/02 06:00 PMCR- 2011/07/01 CRDT- 2010/05/29 06:00 PHST- 2010/05/29 06:00 [entrez] PHST- 2010/05/29 06:00 [pubmed] PHST- 2010/09/02 06:00 [medline] PHST- 2011/07/01 00:00 [pmc-release] AID - BJH8209 [pii] AID - 10.1111/j.1365-2141.2010.08209.x [doi] PST - ppublish SO - Br J Haematol. 2010 Jul;150(2):158-69. doi: 10.1111/j.1365-2141.2010.08209.x. Epub 2010 May 9.