The fully restrained MD simulations were then performed for the two netropsin-DNA complex structures

blation therapy in premenopausal women with breast cancer is associated with a high incidence of bone loss, as high as 13% within 12 months of treatment. Likewise, androgen deprivation therapy triggered significant loss of bone density, about 67% within the first 18 months of treatment. Several in vitro and in vivo experiments suggest that n-3 PUFAs may be effective in slowing down androgen-independent prostate cancer grow. Mice with deletion of the c-Jun Curr Pharmacol Rep. Author manuscript; available in PMC 2016 October 01. Gu et al. Page 10 NH2-terminal kinase or phosphatase and tensin homolog gene can develop invasive AI prostate cancer. Knock-out of Pten expression increased the expression of androgen receptor and prostate cancer cells became more resistant to castration treatment. The increased expression of both androgen receptor mRNA and protein is necessary and sufficient to transform prostate cancer from hormone-sensitive to hormoneinsensitive. In a Pten-null prostate cancer model, we found that n-3 PUFAs decrease the development of castration-resistant tumors as compared with n–6 PUFA. n-3 PUFAs downregulated AR protein levels in both cytosolic and nuclear fractions of tumor cells, but had little effect on AR mRNA levels. n-3 PUFA-induced degradation of AR protein could be blocked by proteasome inhibitor MG132. Reducing the expression of AR significantly reduced prostate cancer cell proliferation. These results indicate that n-3 PUFAs prevent or delay androgen-independent prostate cancer development in part by HC-030031 degrading AR protein in a proteasome-dependent manner. In a mouse CWR22 androgen-independent prostate cancer xenograft model, McEntee et al. found that there was a highly significant positive correlation between the ratio of apoptosis to mitosis and PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/19853262 total n-3 PUFAs in tumors and with the n-3/n-6 PUFA ratio, and an inverse correlation with tissue AA and total n-6 PUFA content. In a cell-based study, Friedriches et al. found that EPA and DHA were able to slow down the growth of LNCaP cells, an androgen-dependent prostate cell line, while AA increased androgen-independent prostate cancer cell growth. Their results established a possible correlation between decreased expression of the androgen receptor and suppression of the Akt/mTOR signaling pathway. In a Pten-null mouse model, where AKT is constitutively active, we also found that n-3 PUFAs can inhibit prostate cancer growth by inhibiting the PI3K/AKT survival pathway. Thus, supplementing dietary n-3 PUFAs in combination with androgen ablation therapy maybe more effective in preventing or inhibiting the development of androgen-independent prostate cancer in patients compared with androgen ablation therapy alone. Similarly, in vitro and in vivo experiments also suggest the potential use of n-3 PUFA to prevent the development of estrogen-independent breast cancer and its metastasis. Regulation of hormonal steroidogenesis involves the metabolism of AA via the 5lipoxygenase pathway. Cooke et al. reported that AA metabolites contribute to steroidogenic acute regulation by engaging, at least in part, the autocrine- or paracrine-activated eicosanoid receptor, OXE-R. DHA treatment partially but significantly decreased progesterone production in OXE-R-expressing cells. These results suggest that DHA can antagonize AA-regulated steroidogenesis through the 5-lipoxygenase pathway. Traditionally, 17-estradiol has been considered as an estrogen receptor- activator to promote breast