Fenretinide induces a new form of dynamin-dependent cell death in pediatric sarcoma.

Cell Death and Differentiation
Eva BrackBeat W Schäfer

Abstract

Alveolar rhabdomyosarcoma (aRMS) is a highly malicious childhood malignancy characterized by specific chromosomal translocations mostly encoding the oncogenic transcription factor PAX3-FOXO1 and therefore also referred to as fusion-positive RMS (FP-RMS). Previously, we have identified fenretinide (retinoic acid p-hydroxyanilide) to affect PAX3-FOXO1 expression levels as well as FP-RMS cell viability. Here, we characterize the mode of action of fenretinide in more detail. First, we demonstrate that fenretinide-induced generation of reactive oxygen species (ROS) depends on complex II of the mitochondrial respiratory chain, since ROS scavenging as well as complexing of iron completely abolished cell death. Second, we co-treated cells with a range of pharmacological inhibitors of specific cell death pathways including z-vad (apoptosis), necrostatin-1 (necroptosis), 3-methyladenine (3-MA) (autophagy), and ferrostatin-1 (ferroptosis) together with fenretinide. Surprisingly, none of these inhibitors was able to prevent cell death. Also genetic depletion of key players in the apoptotic and necroptotic pathway (BAK, BAX, and RIPK1) confirmed the pharmacological data. Interestingly however, electron microscopy of fenretinide-treated cell...Continue Reading

References

Nov 12, 1996·Proceedings of the National Academy of Sciences of the United States of America·M BernasconiB W Schäfer
Mar 14, 1997·Science·K IraniP J Goldschmidt-Clermont
Jan 1, 1997·Advances in Pharmacology·P W MesnerS H Kaufmann
Mar 31, 2000·Experimental Cell Research·S H Kaufmann, W C Earnshaw
Dec 20, 2000·Proceedings of the National Academy of Sciences of the United States of America·S SperandioD E Bredesen
Apr 17, 2001·Apoptosis : an International Journal on Programmed Cell Death·L Coultas, A Strasser
Jul 15, 2003·Journal of Cellular Biochemistry·Penny E LovatChristopher P F Redfern
Nov 1, 2003·Antioxidants & Redox Signaling·Mutay Aslan, Tomris Ozben
May 24, 2005·Cancer Letters·Penny E LovatChristopher P F Redfern
May 27, 2005·Free Radical Biology & Medicine·Wai-Lung Lai, Nai-Sum Wong
Jan 13, 2006·Nature Chemical Biology·Alexei DegterevJunying Yuan
Jul 20, 2006·Apoptosis : an International Journal on Programmed Cell Death·N HailR Lotan
Dec 6, 2006·Cancer Research·James D Orth, Mark A McNiven
Jun 24, 2008·Molecular Cancer Research : MCR·Jean H OvermeyerWilliam A Maltese
Sep 11, 2008·Current Cancer Drug Targets·Simone Fulda
Nov 27, 2009·Cellular and Molecular Life Sciences : CMLS·Roos CuperusAndré B P van Kuilenburg
Mar 31, 2010·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Daniel WilliamsonOlivier Delattre
Mar 8, 2011·Cell·Douglas Hanahan, Robert A Weinberg
May 6, 2011·The Journal of Biological Chemistry·Mehrdad RahmaniyanJacqueline M Kraveka
Dec 14, 2011·Nature Chemical Biology·Candice E PaulsenKate S Carroll
Mar 21, 2012·Cell Biology and Toxicology·Toshihiko AkiKoichi Uemura
May 29, 2012·Cell·Scott J DixonBrent R Stockwell
Jun 30, 2012·Nature Methods·Johannes SchindelinAlbert Cardona
Oct 6, 2012·Experimental and Molecular Pathology·Priya Weerasinghe, L Maximilian Buja
Feb 19, 2013·Pediatric Blood & Cancer·Tobias M DantonelloUNKNOWN Cooperative Weichteilsarkom Studiengruppe
Jul 25, 2013·Frontiers in Oncology·Ashley R P HinsonCorinne M Linardic
Apr 15, 2014·The American Journal of Pathology·William A Maltese, Jean H Overmeyer
Mar 11, 2015·Apoptosis : an International Journal on Programmed Cell Death·Joyce LeeMartin Post
Jun 17, 2016·Molecular & Cellular Oncology·Tom Vanden BerghePeter Vandenabeele
Jun 23, 2016·Oncotarget·Andrey V ShubinSergey V Kostrov
Nov 12, 2016·Oncotarget·Maria Cristina ManaraKatia Scotlandi
Apr 20, 2017·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Ann M MohrbacherBarry J Maurer
Apr 22, 2017·Experimental Biology and Medicine·Jason P CooperMin H Kang
Nov 2, 2017·Nature·Matthew J HangauerMichael T McManus

❮ Previous
Next ❯

Citations

Jul 3, 2021·Frontiers in Oncology·Eva BrackBeat W Schäfer
Jul 13, 2021·Frontiers in Cell and Developmental Biology·Markus RitterHubert H Kerschbaum
Aug 5, 2021·Journal of Bone Oncology·Jiazheng ZhaoHelin Feng

❮ Previous
Next ❯

Methods Mentioned

BETA
xenograft
fluorescence microscopy
flow cytometry
Light microscopy
electron microscopy
Fluorescence
GTPases
genetic interference
fluorescence imaging
PCR

Clinical Trials Mentioned

NCT02163356

Software Mentioned

Fiji
FlowJo
Image Lab
R2
MAPS
GraphPad Prism

Related Concepts

Related Feeds

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis

Autophagosome

An autophagosome is the formation of double-membrane vesicles that involve numerous proteins and cytoplasmic components. These double-membrane vesicles are then terminated at the lysosome where they are degraded. Discover the latest research on autophagosomes here.

Autophagy & Disease

Autophagy is an important cellular process for normal physiology and both elevated and decreased levels of autophagy are associated with disease. Here is the latest research.

Autophagosome

An autophagosome is the formation of double-membrane vesicles that involve numerous proteins and cytoplasmic components. These double-membrane vesicles are then terminated at the lysosome where they are degraded. Discover the latest research on autophagosomes here.

Autophagy & Metabolism

Autophagy preserves the health of cells and tissues by replacing outdated and damaged cellular components with fresh ones. In starvation, it provides an internal source of nutrients for energy generation and, thus, survival. A powerful promoter of metabolic homeostasis at both the cellular and whole-animal level, autophagy prevents degenerative diseases. It does have a downside, however--cancer cells exploit it to survive in nutrient-poor tumors.

Apoptosis in Cancer

Apoptosis is an important mechanism in cancer. By evading apoptosis, tumors can continue to grow without regulation and metastasize systemically. Many therapies are evaluating the use of pro-apoptotic activation to eliminate cancer growth. Here is the latest research on apoptosis in cancer.

Parkinson's Disease & Autophagy (MDS)

Autophagy leads to degradation of damaged proteins and organelles by the lysosome. Impaired autophagy has been implicated in several diseases. Here is the role of autophagy in Parkinson’s disease.

Autophagy & Model Organisms

Autophagy is a cellular process that allows degradation by the lysosome of cytoplasmic components such as proteins or organelles. Here is the latest research on autophagy & model organisms

Related Papers

Journal of the National Cancer Institute
J C Reed
Experimental Cell Research
Penny E LovatChristopher P F Redfern
Apoptosis : an International Journal on Programmed Cell Death
N HailReuben Lotan
© 2021 Meta ULC. All rights reserved