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

School of Medicine

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

15 Scopus citations

Abstract

Inducible phase 2 enzymes constitute a primary line of cellular defense. The oleanane dicyanotriterpenoid 2-cyano-3,12-dioxooleana-1,9(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/cm²/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.

Original language	English (US)
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
State	Published - Mar 21 2008

Keywords

2-cyano-3,12-dioxooleana-1,9(11)-dien-28-onitrile
Heme oxygenase 1
NQO1
SKH-1 hairless mouse

ASJC Scopus subject areas

Biophysics
Biochemistry
Molecular Biology
Cell Biology

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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

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

@article{3ed7ac82187d4b81878eea24f2592d7f,

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-dioxooleana-1,9(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/cm2/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.",

keywords = "2-cyano-3,12-dioxooleana-1,9(11)-dien-28-onitrile, Heme oxygenase 1, NQO1, SKH-1 hairless mouse",

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",

note = "Funding Information: We thank Guosheng Liu for expert technical help and Zachary R. Healy for statistical analysis; the American Cancer Society (IRG 5800543 and RSG-07-157-01-CNE), the Lewis B. and Dorothy Cullman Foundation, and the American Institute for Cancer Research for financial support. ",

year = "2008",

month = mar,

day = "21",

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

language = "English (US)",

volume = "367",

pages = "859--865",

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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

N1 - Funding Information: We thank Guosheng Liu for expert technical help and Zachary R. Healy for statistical analysis; the American Cancer Society (IRG 5800543 and RSG-07-157-01-CNE), the Lewis B. and Dorothy Cullman Foundation, and the American Institute for Cancer Research for financial support.

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-dioxooleana-1,9(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/cm2/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.

AB - Inducible phase 2 enzymes constitute a primary line of cellular defense. The oleanane dicyanotriterpenoid 2-cyano-3,12-dioxooleana-1,9(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/cm2/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.

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

KW - Heme oxygenase 1

KW - NQO1

KW - SKH-1 hairless mouse

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SN - 0006-291X

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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

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