Lipoxidation and cancer immunity

Abstract

Lipoxidation is a well-known reaction between electrophilic carbonyl species, formed during oxidation of lipids, and specific proteins that, in most cases, causes an alteration in proteins function. This can occur under physiological conditions but, in many cases, it has been associated to pathological process, including cancer. Lipoxidation may have an effect in cancer development through their effects in tumour cells, as well as through the alteration of immune components and the consequent modulation of the immune response. The formation of protein adducts affects different proteins in cancer, triggering different mechanism, such as proliferation, cell differentiation and apoptosis, among others, altering cancer progression. The divergent results obtained documented that the formation of lipoxidation adducts can have either anti-carcinogenic or pro-carcinogenic effects, depending on the cell type affected and the specific adduct formed. Moreover, lipoxidation adducts may alter the immune response, consequently causing either positive or negative alterations in cancer progression. Therefore, in this review, we summarize the effects of lipoxidation adducts in cancer cells and immune components and their consequences in the evolution of different types of cancer.

Keywords: Cancer; Immune system; Lipoxidation; Protein adducts.

Graphical abstract

Fig. 1

Diagram illustrating the formation of lipoxidation adducts and their possible effects on the progression of cancer.

Fig. 2

Summary of the possible effects of HNE-protein adducts on different proteins and different cancer cell lines.

Fig. 3

Effects of NFκB inhibition mediated by lipoxidation adducts. High concentration of aldehydes, such as HNE or acrolein, or high concentration of cyclopentenone prostaglandins (cyPG) inhibits IKK activity through the formation of lipoxidation products. IKK inhibition results in the suppression of NFκB activity, hindering the effects triggered by NFkB, such as tumour cells proliferation, suppression of apoptosis, angiogenesis and epithelial-mesenchymal transition, which facilitates distant metastasis. Moreover, cyPG can directly modify NFκB subunits leading to NFκB inhibition, and therefore, the suppression of NFkB effects.