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,

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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.

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KW - Heme oxygenase 1

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KW - SKH-1 hairless mouse

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JO - Biochemical and Biophysical Research Communications

JF - Biochemical and Biophysical Research Communications

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ER -

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

Abstract

Keywords

ASJC Scopus subject areas

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