N-(4-hydroxyphenyl)retinamide promotes apoptosis of resting and proliferating B-cell chronic lymphocytic leukemia cells and potentiates fludarabine and ABT-737 cytotoxicity

Bruno, Silvia; Ghiotto, Fabio; Tenca, Claudya; Mazzarello, Andrea Nicola; Bono, Marı́a Rosa; Luzzi, Paola; Casciaro, Salvatore; Recchia, Anna Grazia; DeCensi, Andrea; Morabito, Fortunato; Fais, Franco

doi:10.1038/leu.2012.98

Cited by 23 publications

(23 citation statements)

References 49 publications

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“…To counteract the ROS adaptation mechanisms, a plausible solution could be the combination of ROS inducers either with another ROS inducer or with compounds that suppress cellular antioxidants, to overcome the threshold useful to induce cell death, The latest approach was tested by using an inhibitor of the scavenger SOD2, 2-Me, in combination with arsenic trioxide in lymphocytic leukemia and urothelial carcinoma cells [46, 47]. Similarly, the combination between the inhibitor of the antiapoptotic protein bcl2 ABT-737 and the ROS inducer, N-(4-hydroxyphenyl) retinamide, or the combination between an NRF2 inhibitor and a glutathione-depleting agents, showed increasing therapeutic efficiency compared to single-agent treatment [48, 49]. Based on these data, several clinical trials of combination treatment between ROS inducers and scavenger inhibitors are ongoing, including a multicenter phase II trial with the iron chelator Triapine and gemcitabine in advanced non-small-cell lung cancer [5].…”

Section: Targeting Oxidative Stress As Anticancer Therapymentioning

confidence: 99%

Oxidative Stress Gene Expression Profile Correlates with Cancer Patient Poor Prognosis: Identification of Crucial Pathways Might Select Novel Therapeutic Approaches

Leone

Roca

Ciardiello

et al. 2017

Oxidative Medicine and Cellular Longevity

114

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The role of altered redox status and high reactive oxygen species (ROS) is still controversial in cancer development and progression. Intracellular levels of ROS are elevated in cancer cells suggesting a role in cancer initiation and progression; on the contrary, ROS elevated levels may induce programmed cell death and have been associated with cancer suppression. Thus, it is crucial to consider the double-face of ROS, for novel therapeutic strategies targeting redox regulatory mechanisms. In this review, in order to derive cancer-type specific oxidative stress genes' profile and their potential prognostic role, we integrated a publicly available oxidative stress gene signature with patient survival data from the Cancer Genome Atlas database. Overall, we found several genes statistically significant associated with poor prognosis in the examined six tumor types. Among them, FoxM1 and thioredoxin reductase1 expression showed the same pattern in four out of six cancers, suggesting their specific critical role in cancer-related oxidative stress adaptation. Our analysis also unveiled an enriched cellular network, highlighting specific pathways, in which many genes are strictly correlated. Finally, we discussed novel findings on the correlation between oxidative stress and cancer stem cells in order to define those pathways to be prioritized in drug development.

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Section: Targeting Oxidative Stress As Anticancer Therapymentioning

confidence: 99%

Oxidative Stress Gene Expression Profile Correlates with Cancer Patient Poor Prognosis: Identification of Crucial Pathways Might Select Novel Therapeutic Approaches

Leone

Roca

Ciardiello

et al. 2017

Oxidative Medicine and Cellular Longevity

114

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“…The synthetic retinoid N-(4-hydroxyphenyl) retinamide (called fenretinide) promotes the intrinsic apoptotic pathway in CLL cells via ROS generation. This is accompanied by Mcl-1 protein degradation resulting from jun N-terminal kinase (JNK) activation [108]. Two other mechanisms have been suggested: inactivation of NF-kB and upregulation of Noxa (which is known to target Mcl-1 for proteasomal degradation).…”

Section: Other Types Of Cll Apoptosis Inducers Fenretinidementioning

confidence: 99%

Untitled

2014

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“…This is accompanied by Mcl-1 protein degradation resulting from jun N-terminal kinase (JNK) activation [108]. Two other mechanisms have been suggested: inactivation of NF-kB and upregulation of Noxa (which is known to target Mcl-1 for proteasomal degradation).…”

Section: Apoptosis Inducers In Cll Cellsmentioning

confidence: 99%

Apoptosis inducers in chronic lymphocytic leukemia

Billard

2013

Oncotarget

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Chronic lymphocytic leukemia (CLL) is characterized by a typical defect in apoptosis and is still an incurable disease. Numerous apoptosis inducers have been described. These synthetic compounds and natural products (mainly derived from plants) display antileukemic properties in vitro and in vivo and some have even been tested in the clinic in CLL. They act through several different mechanisms. Most of them involve proteins of the Bcl-2 family, which are the key regulators in triggering the mitochondrial pathway of caspase-dependent apoptosis. Thus, the Mcl-1/Noxa axis appeared as a target. Here I overview natural and synthetic apoptosis inducers and their mechanisms of action in CLL cells. Opportunities for developing novel, apoptosis-based therapeutics are presented.

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N-(4-hydroxyphenyl)retinamide promotes apoptosis of resting and proliferating B-cell chronic lymphocytic leukemia cells and potentiates fludarabine and ABT-737 cytotoxicity

Cited by 23 publications

References 49 publications

Oxidative Stress Gene Expression Profile Correlates with Cancer Patient Poor Prognosis: Identification of Crucial Pathways Might Select Novel Therapeutic Approaches

Oxidative Stress Gene Expression Profile Correlates with Cancer Patient Poor Prognosis: Identification of Crucial Pathways Might Select Novel Therapeutic Approaches

Untitled

Apoptosis inducers in chronic lymphocytic leukemia

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