He androgen receptor and suppression of the Akt/mTOR signaling pathway.

He 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 PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/19850903 decreased progesterone production in OXE-R-expressing cells. These 153-18-4 web 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 cancer growth. Although inhibition of ER is a successful approach for patients with ER-positive tumors, some patients become resistant to antiestrogen therapy after an initial response. Subsequent studies revealed that E2 could exert its activity through G protein coupled estrogen receptor. Marjon et al. provided the first in vivo evidence that GPER played a critical role in breast tumor growth and metastasis. Cao and colleagues showed that EPA and DHA could switch the effects of estrogen from pro-survival and proliferative to pro-apoptotic in human breast cancer cell lines. EPA and DHA promoted such pro-apoptotic action of estrogen by sensitizing the GPER1-cAMPPKA pathway and blunting the response of EGFR, Erk1/2, and AKT signaling. Based Author Manuscript Author Manuscript Author Manuscript Author Manuscript Curr Pharmacol Rep. Author manuscript; available in PMC 2016 October 01. Gu et al. Page 11 on the known functional interaction between the estrogen and PPAR receptors, Manni et al. tested the hypothesis that the combination of estrogen receptor antagonist DMXB-A site tamoxifen with n-3 PUFAs would have a better antitumor effect than either agent alone. In a chemical carcinogen induced mammary carcinogenesis mouse model, they demonstrated that the combination of tamoxifen and n-3 PUFAs could inhibit tumor development and proliferation to a greater extent than the individual interventions. These results provide a positive indication of better efficacy of escalating n-3 PUFA biologic effects and the pro-apoptotic signaling of estrogen in breast cancer cells, also provide us with a new vision for the potential application of n-3 PUFAs combined with hormone therapy for breast cancer. The sex hormones are particularly important for adults to maintain healthy bones. Loss of hormone production or reduced levels may lead to bone loss. It has been reported that hormonal therapy for women with breast cancer can reduce bone density at a significant rate, at least double that of women during early menopause. For men receiving hormone therapy during prostate cancer treatment, a significant drop of hip bone mineral density occurs frequently, up to 9.6% bone loss in the first year post treatment. A recent study reporte.He 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 PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/19850903 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 cancer growth. Although inhibition of ER is a successful approach for patients with ER-positive tumors, some patients become resistant to antiestrogen therapy after an initial response. Subsequent studies revealed that E2 could exert its activity through G protein coupled estrogen receptor. Marjon et al. provided the first in vivo evidence that GPER played a critical role in breast tumor growth and metastasis. Cao and colleagues showed that EPA and DHA could switch the effects of estrogen from pro-survival and proliferative to pro-apoptotic in human breast cancer cell lines. EPA and DHA promoted such pro-apoptotic action of estrogen by sensitizing the GPER1-cAMPPKA pathway and blunting the response of EGFR, Erk1/2, and AKT signaling. Based Author Manuscript Author Manuscript Author Manuscript Author Manuscript Curr Pharmacol Rep. Author manuscript; available in PMC 2016 October 01. Gu et al. Page 11 on the known functional interaction between the estrogen and PPAR receptors, Manni et al. tested the hypothesis that the combination of estrogen receptor antagonist tamoxifen with n-3 PUFAs would have a better antitumor effect than either agent alone. In a chemical carcinogen induced mammary carcinogenesis mouse model, they demonstrated that the combination of tamoxifen and n-3 PUFAs could inhibit tumor development and proliferation to a greater extent than the individual interventions. These results provide a positive indication of better efficacy of escalating n-3 PUFA biologic effects and the pro-apoptotic signaling of estrogen in breast cancer cells, also provide us with a new vision for the potential application of n-3 PUFAs combined with hormone therapy for breast cancer. The sex hormones are particularly important for adults to maintain healthy bones. Loss of hormone production or reduced levels may lead to bone loss. It has been reported that hormonal therapy for women with breast cancer can reduce bone density at a significant rate, at least double that of women during early menopause. For men receiving hormone therapy during prostate cancer treatment, a significant drop of hip bone mineral density occurs frequently, up to 9.6% bone loss in the first year post treatment. A recent study reporte.