tretinoin has been researched along with Lymphoma--Mantle-Cell* in 7 studies
1 review(s) available for tretinoin and Lymphoma--Mantle-Cell
1 trial(s) available for tretinoin and Lymphoma--Mantle-Cell
6 other study(ies) available for tretinoin and Lymphoma--Mantle-Cell
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Phospholipid scramblase 1 as a critical node at the crossroad between autophagy and apoptosis in mantle cell lymphoma.
Mantle cell lymphoma (MCL) is an aggressive haematological malignancy in which the response to therapy can be limited by aberrantly activated molecular and cellular pathways, among which autophagy was recently listed. Our study shows that the 9-cis-retinoic acid (RA)/Interferon(IFN)-α combination induces protective autophagy in MCL cell lines and primary cultures reducing the extent of drug-induced apoptosis. The treatment significantly up-regulates phospholipid scramblase 1 (PLSCR1), a protein which bi-directionally flips lipids across membranes. In particular, RA/IFN-α combination concomitantly increases PLSCR1 transcription and controls PLSCR1 protein levels via lysosomal degradation. Herein we describe a new function for PLSCR1 as negative regulator of autophagy. Indeed, PLSCR1 overexpression reduced MCL cell susceptibility to autophagy induced by RA/IFN-α, serum deprivation or mTOR pharmacological inhibition. Moreover, PLSCR1 can bind the ATG12/ATG5 complex preventing ATG16L1 recruitment and its full activation, as indicated by co-immunoprecipitation experiments. The combination of doxorubicin or bortezomib with RA/IFN-α strengthened PLSCR1 up-regulation and enhanced apoptosis, as a likely consequence of the blockade of RA/IFN-α-induced autophagy. Immunohistochemical analysis of 32 MCL biopsies revealed heterogeneous expression of PLSCR1 and suggests its possible implication in the response to anticancer therapies, especially to drugs promoting protective autophagy. Topics: Aged; Alitretinoin; Antineoplastic Agents; Apoptosis; Autophagy; Bortezomib; Cell Line, Tumor; Doxorubicin; Drug Synergism; Female; Gene Expression Regulation, Neoplastic; Humans; Interferon-alpha; Lymphoma, Mantle-Cell; Male; Middle Aged; Phospholipid Transfer Proteins; Tretinoin | 2016 |
Novel Nanoscale Delivery Particles Encapsulated with Anticancer Drugs, All-trans Retinoic Acid or Curcumin, Enhance Apoptosis in Lymphoma Cells Predominantly Expressing CD20 Antigen.
Mantle cell lymphoma (MCL), a B-cell lymphoma, pursues a relatively aggressive course, is resistant to long-term remission, and is associated with a poor prognosis. There is a pressing need for innovative treatment approaches against MCL. One such approach is targeted delivery of cytotoxic drugs to MCL cells.. In the current investigation, we pursued a strategy to employ retinoid-based or curcumin-based nanoscale delivery particles, called nanodisks (NDs), for targeted drug delivery to MCL cells (Granta), and human follicular lymphoma (HF-1) cells. The cells were incubated with NDs made of CD20 single-chain variable antibody fragment (scFv)/apolipoprotein A-1 fusion protein, and loaded with either all-trans retinoic acid (ATRA) or curcumin, and cell apoptosis was measured using flow cytometry.. At 10 μM, curcumin-ND induced cell death more effectively than ATRA-ND. Combination of curcumin-ND and ATRA-ND significantly enhanced the biological activity of these drugs against lymphoma cells compared to individual treatments. Topics: Antigens, CD20; Antineoplastic Agents; Apoptosis; Curcumin; Drug Carriers; Humans; Lymphoma, Mantle-Cell; Nanoparticles; Tretinoin | 2015 |
Retinoic acid/alpha-interferon combination inhibits growth and promotes apoptosis in mantle cell lymphoma through Akt-dependent modulation of critical targets.
Mantle cell lymphoma (MCL) is characterized by a profound deregulation of the mechanisms controlling cell-cycle progression and survival. We herein show that the combination of 9-cis-retinoic acid (RA) and IFN-α induces marked antiproliferative and proapoptotic effects in MCL cells through the modulation of critical targets. Particularly, IFN-α enhances RA-mediated G(0)-G(1) cell accumulation by downregulating cyclin D1 and increasing p27(Kip1) and p21(WAF1/Cip1) protein levels. Furthermore, RA/IFN-α combination also induces apoptosis by triggering both caspases-8 and -9 resulting in Bax and Bak activation. In particular, RA/IFN-α treatment downregulates the antiapoptotic Bcl-xL and Bfl-1 proteins and upregulates the proapoptotic BH3-only Noxa protein. Sequestration of Mcl-1 and Bfl-1 by upregulated Noxa results in the activation of Bid, and the consequent induction of apoptosis is inhibited by Noxa silencing. Noxa upregulation is associated with nuclear translocation of the FOXO3a transcription factor as consequence of RA/IFN-α-induced Akt inhibition. Pharmacologic suppression of Akt, but not of TORC1, increases Noxa protein levels and downregulates Bfl-1 protein supporting the conclusion that the inhibition of the Akt pathway, the resulting FOXO3a activation and Noxa upregulation are critical molecular mechanisms underlying RA/IFN-α-dependent MCL cell apoptosis. These results support the potential therapeutic value of RA/IFN-α combination in MCL management. Topics: Aged; Alitretinoin; Antineoplastic Combined Chemotherapy Protocols; Apoptosis; Cell Line, Tumor; Cell Proliferation; Female; Forkhead Box Protein O3; Forkhead Transcription Factors; Humans; Interferon-alpha; Lymphoma, Mantle-Cell; Male; Middle Aged; Phosphoinositide-3 Kinase Inhibitors; Proto-Oncogene Proteins c-akt; Proto-Oncogene Proteins c-bcl-2; Receptors, Retinoic Acid; Retinoic Acid Receptor alpha; Retinoid X Receptors; Tretinoin | 2012 |
All trans retinoic acid nanodisks enhance retinoic acid receptor mediated apoptosis and cell cycle arrest in mantle cell lymphoma.
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. Topics: Antineoplastic Agents; Apoptosis; Benzoates; Cell Cycle; Cell Cycle Proteins; Chromans; Drug Delivery Systems; Drug Evaluation, Preclinical; Guanine Nucleotide Exchange Factors; Humans; Lymphoma, Mantle-Cell; Nanoparticles; Neoplasm Proteins; Nuclear Proteins; Reactive Oxygen Species; Receptors, Retinoic Acid; Retinoid X Receptors; Transcription, Genetic; Tretinoin; Tumor Cells, Cultured | 2010 |
Retinoic acid inhibits the proliferative response induced by CD40 activation and interleukin-4 in mantle cell lymphoma.
Mantle cell lymphoma (MCL) is an aggressive B-cell non-Hodgkin's lymphoma with poor response to therapy and unfavorable prognosis. Here, we show that retinoic acid (RA) isomers significantly inhibit the proliferation of both primary MCL cultures (n = 7) and established cell lines (Granta 519 and SP-53) as shown by [(3)H]thymidine uptake and carboxyfluorescein diacetate succinimidyl ester labeling coupled with cyclin D1 staining. RA induces cell accumulation in G(0)-G(1) together with a marked up-regulation of p27(Kip1) by inhibiting ubiquitination and proteasome-dependent degradation of the protein. The p21(Cip1) inhibitor was also up-regulated by RA in Granta 519 cells, whereas the expression of cyclin D1 is unaffected. Most of RA-induced p27(Kip1) was bound to cyclin D1/cyclin-dependent kinase 4 complexes, probably contributing to the decreased cyclin-dependent kinase 4 kinase activity and pRb hypophosphorylation observed in RA-treated cells. Experiments with receptor-selective ligands indicate that RA receptor alpha cooperates with retinoid X receptors in mediating RA-dependent MCL cell growth inhibition. Notably, RA isomers, and particularly 9-cis-RA, also inhibited the growth-promoting effect induced in primary MCL cells by CD40 activation alone or in combination with interleukin-4. Immunohistochemical analysis showed that significant numbers of CD40L-expressing lymphoid cells are present in lymph node biopsies of MCL patients. These results therefore further strengthen the possibility that triggering of CD40 by infiltrating CD40L+ cells may continuously promote the growth of MCL cells in vivo. On these grounds, our findings that RA inhibits basal MCL proliferation as well as MCL growth-promoting effects exerted by microenvironmental factors make these compounds highly attractive in terms of potential clinical efficacy in this setting. Topics: Aged; CD40 Antigens; CD40 Ligand; Cell Cycle Proteins; Cell Proliferation; Cell Survival; Cyclin D1; Cyclin-Dependent Kinase 4; Cyclin-Dependent Kinase Inhibitor p21; Cyclin-Dependent Kinase Inhibitor p27; Cyclin-Dependent Kinases; Female; Humans; Interleukin-4; Lymphoma, Mantle-Cell; Male; Middle Aged; Proteasome Endopeptidase Complex; Proteasome Inhibitors; Proto-Oncogene Proteins; Receptors, Retinoic Acid; Tretinoin; Tumor Suppressor Proteins | 2005 |
Two cases of therapy-related acute promyelocytic leukemia (t-APL) after mantle cell lymphoma and gestational trophoblastic disease.
We report two cases of secondary acute promyelocytic leukemia (APL). One patient presented with concurrent APL and missed abortion 1 year after etoposide-based chemotherapy for gestational trophoblastic disease. A prolonged complete remission was achieved with standard chemotherapy. An elderly man developed APL 1 year after alkylator-based chemotherapy for mantle cell lymphoma (MCL). A complete clinical and molecular remission was obtained with chemotherapy and all- trans retinoic acid, followed by arsenic consolidation. Concomitant molecular relapse of APL and MCL clones was detected at 1 year, both of which responded to oral arsenic therapy. High-dose epipodophyllin is a dose risk for secondary APL, but alkylating agents may also be implicated. For patients with a history of active malignancy and heavy previous chemotherapy exposure, the use of nontoxic arsenic therapy appeared to be effective and prudent. Topics: Adult; Aged; Antineoplastic Agents, Alkylating; Arsenic Trioxide; Arsenicals; Etoposide; Female; Gestational Trophoblastic Disease; Humans; Leukemia, Promyelocytic, Acute; Lymphoma, Mantle-Cell; Male; Neoplasms, Second Primary; Oxides; Pregnancy; Tretinoin | 2002 |