Department of Internal Medicine Wake Forest School of Medicine, Winston-Salem, NC, USA.
PLoS One. 2012;7(9):e45480. doi: 10.1371/journal.pone.0045480. Epub 2012 Sep 20.
A 15-LOX, it is proposed, suppresses the growth of prostate cancer in part by converting arachidonic, eicosatrienoic, and/or eicosapentaenoic acids to n-6 hydroxy metabolites. These metabolites inhibit the proliferation of PC3, LNCaP, and DU145 prostate cancer cells but only at ≥1-10 µM. We show here that the 15-LOX metabolites of docosahexaenoic acid (DHA), 17-hydroperoxy-, 17-hydroxy-, 10,17-dihydroxy-, and 7,17-dihydroxy-DHA inhibit the proliferation of these cells at ≥0.001, 0.01, 1, and 1 µM, respectively. By comparison, the corresponding 15-hydroperoxy, 15-hydroxy, 8,15-dihydroxy, and 5,15-dihydroxy metabolites of arachidonic acid as well as DHA itself require ≥10-100 µM to do this. Like DHA, the DHA metabolites a) induce PC3 cells to activate a peroxisome proliferator-activated receptor-γ (PPARγ) reporter, express syndecan-1, and become apoptotic and b) are blocked from slowing cell proliferation by pharmacological inhibition or knockdown of PPARγ or syndecan-1. The DHA metabolites thus slow prostate cancer cell proliferation by engaging the PPARγ/syndecan-1 pathway of apoptosis and thereby may contribute to the prostate cancer-suppressing effects of not only 15-LOX but also dietary DHA.
15-脂氧合酶（15-LOX）通过将花生四烯酸、二十碳三烯酸和/或二十碳五烯酸转化为 n-6 羟基代谢物，从而抑制前列腺癌的生长。这些代谢物抑制 PC3、LNCaP 和 DU145 前列腺癌细胞的增殖，但仅在≥1-10μM 时有效。我们在此表明，二十二碳六烯酸（DHA）的 15-LOX 代谢物 17-过氧、17-羟、10,17-二羟和 7,17-二羟-DHA 在≥0.001、0.01、1 和 1μM 时分别抑制这些细胞的增殖。相比之下，相应的花生四烯酸的 15-过氧、15-羟、8,15-二羟和 5,15-二羟代谢物以及 DHA 本身需要≥10-100μM 才能发挥作用。与 DHA 一样，DHA 代谢物 a）诱导 PC3 细胞激活过氧化物酶体增殖物激活受体-γ（PPARγ）报告基因，表达 syndecan-1，并发生凋亡，b）通过药理学抑制或敲低 PPARγ 或 syndecan-1 阻断其对细胞增殖的抑制作用。因此，DHA 代谢物通过激活 PPARγ/syndecan-1 凋亡途径来减缓前列腺癌细胞的增殖，从而可能有助于不仅是 15-LOX，还有饮食中的 DHA 抑制前列腺癌的作用。
