Specific and prolonged proteasome inhibition dictates apoptosis induction by marizomib and its analogs

Claudia P. Miller; Christa A. Manton; Randal Hale; La Keisha Debose; Venkat R. Macherla; Barbara C. Potts; Michael A. Palladino; Joya Chandra

doi:10.1016/j.cbi.2011.08.005

Specific and prolonged proteasome inhibition dictates apoptosis induction by marizomib and its analogs

Claudia P. Miller, Christa A. Manton, Randal Hale, La Keisha Debose, Venkat R. Macherla, Barbara C. Potts, Michael A. Palladino, Joya Chandra

Pediatrics

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19 Scopus citations

Abstract

Marizomib (NPI-0052) is a naturally derived irreversible proteasome inhibitor that potently induces apoptosis via a caspase-8 and ROS-dependent mechanism in leukemia cells. We aim to understand the relationship between the irreversible inhibition of the proteasome and induction of cell death in leukemia cells by using analogs of marizomib that display reversible and irreversible properties. We highlight the importance of sustained inhibition of at least two proteasome activities as being key permissive events for the induction of the apoptotic process in leukemia cells. These data provide the basis for the development of new approaches to generate more effective anti-proteasome therapies.

Original language	English (US)
Pages (from-to)	58-68
Number of pages	11
Journal	Chemico-Biological Interactions
Volume	194
Issue number	1
DOIs	https://doi.org/10.1016/j.cbi.2011.08.005
State	Published - Oct 15 2011

Keywords

Apoptosis
Caspase-8
Leukemia
Oxidative stress
Proteasome inhibitors

ASJC Scopus subject areas

Toxicology

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10.1016/j.cbi.2011.08.005

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title = "Specific and prolonged proteasome inhibition dictates apoptosis induction by marizomib and its analogs",

abstract = "Marizomib (NPI-0052) is a naturally derived irreversible proteasome inhibitor that potently induces apoptosis via a caspase-8 and ROS-dependent mechanism in leukemia cells. We aim to understand the relationship between the irreversible inhibition of the proteasome and induction of cell death in leukemia cells by using analogs of marizomib that display reversible and irreversible properties. We highlight the importance of sustained inhibition of at least two proteasome activities as being key permissive events for the induction of the apoptotic process in leukemia cells. These data provide the basis for the development of new approaches to generate more effective anti-proteasome therapies.",

keywords = "Apoptosis, Caspase-8, Leukemia, Oxidative stress, Proteasome inhibitors",

author = "Miller, {Claudia P.} and Manton, {Christa A.} and Randal Hale and Debose, {La Keisha} and Macherla, {Venkat R.} and Potts, {Barbara C.} and Palladino, {Michael A.} and Joya Chandra",

note = "Funding Information: This work was supported, in part, by the National Institutes of Health with Grant R01 CA115811 to J.C. and fellowship F31CA123645-03 to C.P.M. The Cancer Prevention and Research Institute of Texas Research Training Award RP101502 provided additional support for C.A.M. We thank Rao Manam for providing some of the analogs used in this study. We also acknowledge Raelene Endersby for her assistance with formatting figures and Mary Irwin for her help with use of Prism software.",

year = "2011",

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day = "15",

doi = "10.1016/j.cbi.2011.08.005",

language = "English (US)",

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T1 - Specific and prolonged proteasome inhibition dictates apoptosis induction by marizomib and its analogs

AU - Miller, Claudia P.

AU - Manton, Christa A.

AU - Hale, Randal

AU - Debose, La Keisha

AU - Macherla, Venkat R.

AU - Potts, Barbara C.

AU - Palladino, Michael A.

AU - Chandra, Joya

N1 - Funding Information: This work was supported, in part, by the National Institutes of Health with Grant R01 CA115811 to J.C. and fellowship F31CA123645-03 to C.P.M. The Cancer Prevention and Research Institute of Texas Research Training Award RP101502 provided additional support for C.A.M. We thank Rao Manam for providing some of the analogs used in this study. We also acknowledge Raelene Endersby for her assistance with formatting figures and Mary Irwin for her help with use of Prism software.

PY - 2011/10/15

Y1 - 2011/10/15

N2 - Marizomib (NPI-0052) is a naturally derived irreversible proteasome inhibitor that potently induces apoptosis via a caspase-8 and ROS-dependent mechanism in leukemia cells. We aim to understand the relationship between the irreversible inhibition of the proteasome and induction of cell death in leukemia cells by using analogs of marizomib that display reversible and irreversible properties. We highlight the importance of sustained inhibition of at least two proteasome activities as being key permissive events for the induction of the apoptotic process in leukemia cells. These data provide the basis for the development of new approaches to generate more effective anti-proteasome therapies.

AB - Marizomib (NPI-0052) is a naturally derived irreversible proteasome inhibitor that potently induces apoptosis via a caspase-8 and ROS-dependent mechanism in leukemia cells. We aim to understand the relationship between the irreversible inhibition of the proteasome and induction of cell death in leukemia cells by using analogs of marizomib that display reversible and irreversible properties. We highlight the importance of sustained inhibition of at least two proteasome activities as being key permissive events for the induction of the apoptotic process in leukemia cells. These data provide the basis for the development of new approaches to generate more effective anti-proteasome therapies.

KW - Apoptosis

KW - Caspase-8

KW - Leukemia

KW - Oxidative stress

KW - Proteasome inhibitors

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Specific and prolonged proteasome inhibition dictates apoptosis induction by marizomib and its analogs

Abstract

Keywords

ASJC Scopus subject areas

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