17α-Ethynyl-5α-androstane-3α, 17β-diol Treatment of MNU-Induced Mammary Cancer in Rats
N-methyl-N-nitrosourea (MNU) induces estrogen-dependent mammary tumors in female Lewis rats. We explored the antineoplastic activity of a synthetic androstane derivative, 17α-ethynyl-5α-androstane-3α, 17β-diol (HE3235), as a single agent or in combination with docetaxel compared to tamoxifen, anast...
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| Format: | Article |
| Language: | English |
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Wiley
2011-01-01
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| Series: | International Journal of Breast Cancer |
| Online Access: | http://dx.doi.org/10.4061/2011/618757 |
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| _version_ | 1832553587017777152 |
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| author | Clarence N. Ahlem James M. Frincke Steven K. White Christopher L. Reading Richard J. Trauger Rajkumar Lakshmanaswamy |
| author_facet | Clarence N. Ahlem James M. Frincke Steven K. White Christopher L. Reading Richard J. Trauger Rajkumar Lakshmanaswamy |
| author_sort | Clarence N. Ahlem |
| collection | DOAJ |
| description | N-methyl-N-nitrosourea (MNU) induces estrogen-dependent mammary tumors in female
Lewis rats. We explored the antineoplastic activity of a synthetic androstane derivative,
17α-ethynyl-5α-androstane-3α, 17β-diol (HE3235), as a single agent or in combination
with docetaxel compared to tamoxifen, anastrazole, and docetaxel monotherapies against
MNU-induced mammary tumors in female Lewis rats. Treatment with HE3235 alone
rapidly reduced tumor burden, similar in effect to tamoxifen and anastrozole. The
combination of HE3235 with docetaxel was more effective than any single agent, although
without apparent toxicity. Only HE3235 or HE3235 plus docetaxel continued to suppress
tumor growth after cessation of treatment. HE3235 treatment increased
immunohistochemical markers of apoptosis and expression of proapoptotic genes and
estrogen receptor beta and decreased expression of antiapoptotic genes, androgen
receptor, and estrogen receptor alpha. These data warrant clinical investigation of HE3235
for breast cancer treatment. |
| format | Article |
| id | doaj-art-0f37c0cee40646c3a2dc51e5385f8237 |
| institution | Kabale University |
| issn | 2090-3189 |
| language | English |
| publishDate | 2011-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | International Journal of Breast Cancer |
| spelling | doaj-art-0f37c0cee40646c3a2dc51e5385f82372025-02-03T05:53:36ZengWileyInternational Journal of Breast Cancer2090-31892011-01-01201110.4061/2011/61875761875717α-Ethynyl-5α-androstane-3α, 17β-diol Treatment of MNU-Induced Mammary Cancer in RatsClarence N. Ahlem0James M. Frincke1Steven K. White2Christopher L. Reading3Richard J. Trauger4Rajkumar Lakshmanaswamy5Harbor BioSciences, Inc., 9171 Towne Centre Drive, Suite 180, San Diego, CA 92122, USAHarbor BioSciences, Inc., 9171 Towne Centre Drive, Suite 180, San Diego, CA 92122, USAHarbor BioSciences, Inc., 9171 Towne Centre Drive, Suite 180, San Diego, CA 92122, USAHarbor BioSciences, Inc., 9171 Towne Centre Drive, Suite 180, San Diego, CA 92122, USAHarbor BioSciences, Inc., 9171 Towne Centre Drive, Suite 180, San Diego, CA 92122, USACenter of Excellence in Cancer Research, Department of Biomedical Sciences, Texas Tech University Health Sciences Center, 4800 Alberta Ave, El Paso, TX 79905, USAN-methyl-N-nitrosourea (MNU) induces estrogen-dependent mammary tumors in female Lewis rats. We explored the antineoplastic activity of a synthetic androstane derivative, 17α-ethynyl-5α-androstane-3α, 17β-diol (HE3235), as a single agent or in combination with docetaxel compared to tamoxifen, anastrazole, and docetaxel monotherapies against MNU-induced mammary tumors in female Lewis rats. Treatment with HE3235 alone rapidly reduced tumor burden, similar in effect to tamoxifen and anastrozole. The combination of HE3235 with docetaxel was more effective than any single agent, although without apparent toxicity. Only HE3235 or HE3235 plus docetaxel continued to suppress tumor growth after cessation of treatment. HE3235 treatment increased immunohistochemical markers of apoptosis and expression of proapoptotic genes and estrogen receptor beta and decreased expression of antiapoptotic genes, androgen receptor, and estrogen receptor alpha. These data warrant clinical investigation of HE3235 for breast cancer treatment.http://dx.doi.org/10.4061/2011/618757 |
| spellingShingle | Clarence N. Ahlem James M. Frincke Steven K. White Christopher L. Reading Richard J. Trauger Rajkumar Lakshmanaswamy 17α-Ethynyl-5α-androstane-3α, 17β-diol Treatment of MNU-Induced Mammary Cancer in Rats International Journal of Breast Cancer |
| title | 17α-Ethynyl-5α-androstane-3α, 17β-diol Treatment of MNU-Induced Mammary Cancer in Rats |
| title_full | 17α-Ethynyl-5α-androstane-3α, 17β-diol Treatment of MNU-Induced Mammary Cancer in Rats |
| title_fullStr | 17α-Ethynyl-5α-androstane-3α, 17β-diol Treatment of MNU-Induced Mammary Cancer in Rats |
| title_full_unstemmed | 17α-Ethynyl-5α-androstane-3α, 17β-diol Treatment of MNU-Induced Mammary Cancer in Rats |
| title_short | 17α-Ethynyl-5α-androstane-3α, 17β-diol Treatment of MNU-Induced Mammary Cancer in Rats |
| title_sort | 17α ethynyl 5α androstane 3α 17β diol treatment of mnu induced mammary cancer in rats |
| url | http://dx.doi.org/10.4061/2011/618757 |
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