A dicyanotriterpenoid induces cytoprotective enzymes and reduces multiplicity of skin tumors in UV-irradiated mice

Albena T. Dinkova-Kostova; Stephanie N. Jenkins; Scott L. Wehage; David L. Huso; Andrea L. Benedict; Katherine K. Stephenson; Jed W. Fahey; Hua Liu; Karen T. Liby; Tadashi Honda; Gordon W. Gribble; Michael B. Sporn; Paul Talalay

doi:10.1016/j.bbrc.2008.01.026

A dicyanotriterpenoid induces cytoprotective enzymes and reduces multiplicity of skin tumors in UV-irradiated mice

Albena T. Dinkova-Kostova, Stephanie N. Jenkins, Scott L. Wehage, David L. Huso, Andrea L. Benedict, Katherine K. Stephenson, Jed W. Fahey, Hua Liu, Karen T. Liby, Tadashi Honda, Gordon W. Gribble, Michael B. Sporn, Paul Talalay

Research output: Contribution to journal › Article › peer-review

17 Citations (Scopus)

Abstract

Inducible phase 2 enzymes constitute a primary line of cellular defense. The oleanane dicyanotriterpenoid 2-cyano-3,12-dioxooleana1,9(11)-dien-28-onitrile (TP-225) is a very potent inducer of these systems. Topical application of TP-225 to SKH-1 hairless mice increases the levels of NAD(P)H-quinone acceptor oxidoreductase 1 (NQO1) and heme oxygenase 1 (HO-1) and protects against UV radiation-induced dermal thickening. Daily topical treatments of 10 nmol of TP-225 to the backs of mice that were previously subjected to low-level chronic UVB radiation (30 mJ/cm(2)/session, twice a week for 17 weeks), led to 50% reduction in multiplicity of skin tumors. In addition, the total tumor burden of squamous cell carcinomas was reduced by 5.5-fold. The identification of new agents for protection against UV radiation-induced skin cancer and understanding of their mechanism(s) of action is especially important in view of the fact that human skin cancers represent a significant source of increasing morbidity and mortality. (c) 2008 Elsevier Inc. All rights reserved.

Original language	English
Pages (from-to)	859-865
Number of pages	7
Journal	Biochemical and Biophysical Research Communications
Volume	367
Issue number	4
DOIs	https://doi.org/10.1016/j.bbrc.2008.01.026
Publication status	Published - 21 Mar 2008

Keywords

2-cyano-3,12-dioxooleana-1,9(11)-dien-28-onitrile
Heme oxygenase 1
NQO1
SKH-1 hairless mouse
BROCCOLI SPROUT EXTRACTS
NITRIC-OXIDE PRODUCTION
PHASE-2 RESPONSE
HEME OXYGENASE-1
INDUCTION
CARCINOGENESIS
SULFORAPHANE
INHIBITION
PROTECTION
STRESS

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.bbrc.2008.01.026

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Dinkova-Kostova, A. T., Jenkins, S. N., Wehage, S. L., Huso, D. L., Benedict, A. L., Stephenson, K. K., Fahey, J. W., Liu, H., Liby, K. T., Honda, T., Gribble, G. W., Sporn, M. B., & Talalay, P. (2008). A dicyanotriterpenoid induces cytoprotective enzymes and reduces multiplicity of skin tumors in UV-irradiated mice. Biochemical and Biophysical Research Communications, 367(4), 859-865. https://doi.org/10.1016/j.bbrc.2008.01.026

@article{354a09286fad484084004c38d65ec910,

title = "A dicyanotriterpenoid induces cytoprotective enzymes and reduces multiplicity of skin tumors in UV-irradiated mice",

abstract = "Inducible phase 2 enzymes constitute a primary line of cellular defense. The oleanane dicyanotriterpenoid 2-cyano-3,12-dioxooleana1,9(11)-dien-28-onitrile (TP-225) is a very potent inducer of these systems. Topical application of TP-225 to SKH-1 hairless mice increases the levels of NAD(P)H-quinone acceptor oxidoreductase 1 (NQO1) and heme oxygenase 1 (HO-1) and protects against UV radiation-induced dermal thickening. Daily topical treatments of 10 nmol of TP-225 to the backs of mice that were previously subjected to low-level chronic UVB radiation (30 mJ/cm(2)/session, twice a week for 17 weeks), led to 50% reduction in multiplicity of skin tumors. In addition, the total tumor burden of squamous cell carcinomas was reduced by 5.5-fold. The identification of new agents for protection against UV radiation-induced skin cancer and understanding of their mechanism(s) of action is especially important in view of the fact that human skin cancers represent a significant source of increasing morbidity and mortality. (c) 2008 Elsevier Inc. All rights reserved.",

keywords = "2-cyano-3,12-dioxooleana-1,9(11)-dien-28-onitrile, Heme oxygenase 1, NQO1, SKH-1 hairless mouse, BROCCOLI SPROUT EXTRACTS, NITRIC-OXIDE PRODUCTION, PHASE-2 RESPONSE, HEME OXYGENASE-1, INDUCTION, CARCINOGENESIS, SULFORAPHANE, INHIBITION, PROTECTION, STRESS",

author = "Dinkova-Kostova, {Albena T.} and Jenkins, {Stephanie N.} and Wehage, {Scott L.} and Huso, {David L.} and Benedict, {Andrea L.} and Stephenson, {Katherine K.} and Fahey, {Jed W.} and Hua Liu and Liby, {Karen T.} and Tadashi Honda and Gribble, {Gordon W.} and Sporn, {Michael B.} and Paul Talalay",

year = "2008",

month = mar,

day = "21",

doi = "10.1016/j.bbrc.2008.01.026",

language = "English",

volume = "367",

pages = "859--865",

journal = "Biochemical and Biophysical Research Communications",

issn = "0006-291X",

publisher = "Elsevier",

number = "4",

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Dinkova-Kostova, AT, Jenkins, SN, Wehage, SL, Huso, DL, Benedict, AL, Stephenson, KK, Fahey, JW, Liu, H, Liby, KT, Honda, T, Gribble, GW, Sporn, MB & Talalay, P 2008, 'A dicyanotriterpenoid induces cytoprotective enzymes and reduces multiplicity of skin tumors in UV-irradiated mice', Biochemical and Biophysical Research Communications, vol. 367, no. 4, pp. 859-865. https://doi.org/10.1016/j.bbrc.2008.01.026

TY - JOUR

T1 - A dicyanotriterpenoid induces cytoprotective enzymes and reduces multiplicity of skin tumors in UV-irradiated mice

AU - Dinkova-Kostova, Albena T.

AU - Jenkins, Stephanie N.

AU - Wehage, Scott L.

AU - Huso, David L.

AU - Benedict, Andrea L.

AU - Stephenson, Katherine K.

AU - Fahey, Jed W.

AU - Liu, Hua

AU - Liby, Karen T.

AU - Honda, Tadashi

AU - Gribble, Gordon W.

AU - Sporn, Michael B.

AU - Talalay, Paul

PY - 2008/3/21

Y1 - 2008/3/21

N2 - Inducible phase 2 enzymes constitute a primary line of cellular defense. The oleanane dicyanotriterpenoid 2-cyano-3,12-dioxooleana1,9(11)-dien-28-onitrile (TP-225) is a very potent inducer of these systems. Topical application of TP-225 to SKH-1 hairless mice increases the levels of NAD(P)H-quinone acceptor oxidoreductase 1 (NQO1) and heme oxygenase 1 (HO-1) and protects against UV radiation-induced dermal thickening. Daily topical treatments of 10 nmol of TP-225 to the backs of mice that were previously subjected to low-level chronic UVB radiation (30 mJ/cm(2)/session, twice a week for 17 weeks), led to 50% reduction in multiplicity of skin tumors. In addition, the total tumor burden of squamous cell carcinomas was reduced by 5.5-fold. The identification of new agents for protection against UV radiation-induced skin cancer and understanding of their mechanism(s) of action is especially important in view of the fact that human skin cancers represent a significant source of increasing morbidity and mortality. (c) 2008 Elsevier Inc. All rights reserved.

AB - Inducible phase 2 enzymes constitute a primary line of cellular defense. The oleanane dicyanotriterpenoid 2-cyano-3,12-dioxooleana1,9(11)-dien-28-onitrile (TP-225) is a very potent inducer of these systems. Topical application of TP-225 to SKH-1 hairless mice increases the levels of NAD(P)H-quinone acceptor oxidoreductase 1 (NQO1) and heme oxygenase 1 (HO-1) and protects against UV radiation-induced dermal thickening. Daily topical treatments of 10 nmol of TP-225 to the backs of mice that were previously subjected to low-level chronic UVB radiation (30 mJ/cm(2)/session, twice a week for 17 weeks), led to 50% reduction in multiplicity of skin tumors. In addition, the total tumor burden of squamous cell carcinomas was reduced by 5.5-fold. The identification of new agents for protection against UV radiation-induced skin cancer and understanding of their mechanism(s) of action is especially important in view of the fact that human skin cancers represent a significant source of increasing morbidity and mortality. (c) 2008 Elsevier Inc. All rights reserved.

KW - 2-cyano-3,12-dioxooleana-1,9(11)-dien-28-onitrile

KW - Heme oxygenase 1

KW - NQO1

KW - SKH-1 hairless mouse

KW - BROCCOLI SPROUT EXTRACTS

KW - NITRIC-OXIDE PRODUCTION

KW - PHASE-2 RESPONSE

KW - HEME OXYGENASE-1

KW - INDUCTION

KW - CARCINOGENESIS

KW - SULFORAPHANE

KW - INHIBITION

KW - PROTECTION

KW - STRESS

U2 - 10.1016/j.bbrc.2008.01.026

DO - 10.1016/j.bbrc.2008.01.026

M3 - Article

C2 - 18206646

SN - 0006-291X

VL - 367

SP - 859

EP - 865

JO - Biochemical and Biophysical Research Communications

JF - Biochemical and Biophysical Research Communications

IS - 4

ER -

A dicyanotriterpenoid induces cytoprotective enzymes and reduces multiplicity of skin tumors in UV-irradiated mice

Abstract

Keywords

UN SDGs

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