Lipid Peroxidation in Cancer Cells: Chemical and Physical Studies ^a

Abstract

Our studies on the biochemical composition and the structural organization of smooth and rough endoplasmic reticulum isolated from Morris hepatomas 9618A and 3924A confirm the results obtained employing the total microsomal fraction. We have definitely established the following facts: (1) Tumor subcellular organelles exhibit the very low degree of peroxidizability that has been shown to be related to the growth rate of the tumor. (2) Associated with such a low susceptibility to peroxidation are (a) changed lipid composition of cellular membranes, whose content in polyunsaturated fatty acid is markedly decreased, and (b) changed static and dynamic properties of the membrane. Previously it was also found that cellular oxy-radical scavenging enzymes are markedly reduced. From these data, it is possible to infer that tumor membranes are altered structurally and functionally in part as the result of an oxy-radical-induced damage that occurs in vivo under conditions of oxygen toxicity. This seems to be supported by recent findings that the spontaneous increase in growth rate of the originally very slow-growing Morris hepatoma 9618A results also in the loss of cytochrome P-450 (an important intramembraneous propagator of lipid peroxidation) as well as of C20:4 and C22:6. Studies performed by GLC and GC-MS on the fatty acid residues of phospholipids of rat liver microsomes show the presence of C20:3-OH and C18:1-OH, but no hydroxyl derivatives of low molecular weight aldehydes. The hydroxyl derivatives of arachidonic acid and linoleic acid are present in much smaller amounts in the microsomes isolated from H9618A and H3924A.

Histone deacetylase 1: a target of 9-hydroxystearic acid in the inhibition of cell growth in human colon cancer

“…9-Hydroxystearic acid (9-HSA) belongs to the class of endogenous lipid peroxidation by-products that are greatly diminished in tumors and therefore become unable to exert their normal controlling functions on cell division (1). Indeed, in HT29 cells, exogenous administration of 9-HSA at micromolar concentrations results in a significant inhibition of proliferation rate as well as a significant increase of p53-independent p21 WAF1 expression (2).…”

Gas chromatography/mass spectrometric assay of endogenous cellular lipid peroxidation products: quantitative analysis of 9‐ and 10‐hydroxystearic acids

“…Growing evidence points to the involvement of long‐chain lipid peroxidation by‐products in the control of cell proliferation and tumour growth. Previous studies have shown that the endogenous production of two hydroxy derivatives of linoleic and arachidonic acids was greatly diminished in experimental hepatomas compared to control tissue, and was related to the cellular prooxidant/antioxidant balance, the proliferative status, and the grade of differentiation of the tumours 1. The investigation was then extended to cell lines, trying to identify new endogenous oxidation products of biological interest.…”

Selective colocalization of lipid peroxidation and protein thiol loss in chemically induced hepatic preneoplastic lesions: the role of γ-glutamyltranspeptidase activity

“…In fact, the observed decrease of oxidizable lipids in hepatocyte nodules (Figs. 6, 7) is likely the result of their consumption during previous LPO Schaur et al 1987;Masotti et al 1988b). Thus, the lower inducibility of lipid oxidatin by H202 plus iron(II) in hepatocyte nodules can be interpreted as a further indication, besides the loss of protein thiols, of an ongoing lip- Altogether, the data reported in the present study point to the possibility that a process of LPO takes place continuously in vivo during chemical hepatocarcinogenesis, with a strict localization at the GGT-rich areas of chemically transformed cells.…”