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. 2006 Mar 27:5:9.
doi: 10.1186/1477-3163-5-9.

The yin and yang of 15-lipoxygenase-1 and delta-desaturases: dietary omega-6 linoleic acid metabolic pathway in prostate

Uddhav Kelavkar  1 , Yan Lin, Doug Landsittel, Uma Chandran, Rajiv Dhir
Affiliations

The yin and yang of 15-lipoxygenase-1 and delta-desaturases: dietary omega-6 linoleic acid metabolic pathway in prostate

Uddhav Kelavkar et al. J Carcinog. .

Abstract

One of the major components in high-fat diets (Western diet) is the omega (omega, n)-6 polyunsaturated fatty acid (PUFA) called linoleic acid (LA). Linoleic acid is the precursor for arachidonic acid (AA). These fatty acids are metabolized to an array of eicosanoids and prostaglandins depending upon the enzymes in the pathway. Aberrant expression of the catabolic enzymes such as cyclooxygenases (COX-1 and/or -2) or lipoxygenases (5-LO, 12-LO, 15-LO-1, and 15-LO-2) that convert PUFA either AA and/or LA to bioactive lipid metabolites appear to significantly contribute to the development of PCa. However, PUFA and its cellular interactions in PCa are poorly understood. We therefore examined the mRNA levels of key enzymes involved in the LA and AA pathways in 18 human donor (normal) prostates compared to 60 prostate tumors using the Affymetrix U95Av2 chips. This comparative (normal donor versus prostate cancer) study showed that: 1) the level of 15-LO-1 expression (the key enzyme in the LA pathway) is low (P < 0.001), whereas the levels of delta-5 desaturase (P < 0.001, the key enzyme in the AA pathway), delta-6 desaturase (P = 0.001), elongase (P = 0.16) and 15-lipoxygenase-2 (15-LO-2, P = 0.74) are higher in donor (normal) prostates, and 2) Contrary to the observation in the normal tissues, significantly high levels of only 15-LO-1; whereas low levels of delta-6 desaturase, elongase, delta-5 desaturase and 15-LO-2 respectively, were observed in PCa tissues. Although the cyclooxygenase (COX)-1 and COX-2 mRNA levels were high in PCa, no significant differences were observed when compared in donor tissues. Our study underscores the importance of promising dietary intervention agents such as the omega-3 fatty acids as substrate competitors of LA/AA, aimed primarily at high 15-LO-1 and COX-2 as the molecular targets in PCa initiation and/or progression.

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Figure 1
Omega-6 and -3 fatty acids & Prostate Cancer.
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References

    1. American Cancer Society-Cancer facts and figures 2005
    1. Chan JM, Jou RM, Carroll PR. The relative impact and future burden of prostate cancer in the United States. J Urol. 2004;172:S13–S17. doi: 10.1097/01.ju.0000142068.66876.53. - DOI - PubMed
    1. Brawley OW, Knopf K, Thompson I. The epidemiology of prostate cancer part II: the risk factors. Semin Urol Oncol. 1998;16:193–201. - PubMed
    1. Carter HB, Coffey DS. The prostate: an increasing medical problem. Prostate. 1990;16:39–48. - PubMed
    1. Gann PH, Hennekens CH, Sacks FM, Grodstein F, Giovannucci EL, Stampfer MJ. Prospective study of plasma fatty acids and risk of prostate cancer. J Natl Cancer Inst. 1994;86:281–286. - PubMed