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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| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
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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| Summary: | 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. |
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| ISSN: | 2090-3189 |