15-Lipoxygenase and its metabolites in the pathogenesis of breast cancer: A double-edged sword

Abstract

Abstract15-lipoxygenase is one of the key enzymes for the metabolism of unsaturated fatty acids that its manipulation has been proposed recently as a new molecular target for regulating cancer cell growth. Aberrant expression of 15-lipoxygenase enzyme seems to play an indicative role in the pathology of different cancer types, tumor progression, metastasis, or apoptosis. Based on the fact that breast cancer is one of the most common cancers that imposes a burden of mortality in women also, on the other hand, evidence in experimental models and human studies indicate the emerging role of the 15-lipoxygenase pathway in breast cancer pathogenesis, we present a review of recent findings related to the role of 15- lipoxygenase enzyme and metabolites in breast cancer growth, apoptosis, metastasis, and invasion as well as their local and circulating expression pattern in patients with breast cancer. Our review supports the emerging role of 15- lipoxygenase in molecular and cellular processes regulating breast tumor cell fate with both positive and negative effects.

Quantitative and qualitative determination of carotenoids and polyphenolics compounds in selected cultivars of Prunus persica L. and their ability to in vitro inhibit lipoxygenase, cholinoesterase, α-amylase, α-glucosidase and pancreatic lipase

“…15-LOX is one of the key enzymes for the metabolism of unsaturated fatty acids. Aberrant expression of the 15-LOX enzyme seems to play an indicative role in the pathology of different cancers, metastasis, or tumor progression; therefore, it is important to find effective inhibitors of this enzyme ( Vaezi et al, 2021 ).…”

Arachidonate 15-lipoxygenase type B: Regulation, function, and its role in pathophysiology

“…This notion is reflected in prostate cancer, where ALOX15's substrate preference to LA is reported along with differential effects of 15-HETE and 13-HODE (Hsi et al, 2002). Similar to prostate cancer, a lower expression of ALOX15B has been detected in breast cancer in comparison to normal breast tissue (Nony et al, 2005;Jiang et al, 2006;Wu et al, 2021), in addition to 15-HETE being reduced (Subbarayan et al, 2005;Vaezi et al, 2021).…”

“…Investigations of ALOX15B in cancer have predominantly focused on a role as a tumor suppressor; however, conflicting evidence suggests that tissue-dependent regulation and functions are apparent. Whereas in prostate ( Shappell et al, 1999 ; Bhatia et al, 2003 ; Tang et al, 2004 ; Suraneni et al, 2010 ) and breast carcinoma ( Kort et al, 1992 ; Jiang et al, 2006 ; Vaezi et al, 2021 ; Wu et al, 2021 ) ALOX15B is downregulated, expression of ALOX15B in colorectal cancer is associated with a poorer prognosis ( Yuan et al, 2020 ). Table 3 provides further insight into expression alterations of ALOX15B or its products 15-HETE and 13-HODE in different types of cancers.…”

“…While normal prostate epithelium expresses ALOX15B but not ALOX15 in the luminal compartment ( Subbarayan et al, 2006 ), expression of ALOX15B was lost in prostate cancer ( Shappell et al, 1999 ; Bhatia et al, 2005 ) as well as associated cell lines ( Tang et al, 2002 ), and also 15-HETE production was found to be reduced ( Shappell et al, 2001b ). Recently Vaezi et al (2021) reviewed the role of 15-LOXs in breast cancer, summarizing the contrasting roles of ALOX15B and ALOX15, being negative and positive respectively, towards tumor formation. This notion is reflected in prostate cancer, where ALOX15’s substrate preference to LA is reported along with differential effects of 15-HETE and 13-HODE ( Hsi et al, 2002 ).…”

“…As biologically active lipid mediators, the produced fatty acids are involved in a wide range of acute and chronic pathological conditions ( Kühn et al, 2015 ). Depending on the metabolite, its effect and implication can be ambiguous: anti-inflammatory, pro-resolving, pro-inflammatory ( Fogh et al, 1988 ), as well as pro- or anti-tumorigenic ( Vaezi et al, 2021 ). Although initially classified according to their positional specificity of AA oxygenation, the six functional human LOX enzymes ALOX15B, ALOX15, ALOX5, ALOX12, ALOX12B, and ALOXE3 can also oxygenate other PUFA substrates i.e.…”