Effects of the lipidperoxidation product 4-hydroxynonenal and related aldehydes on proliferation and viability of cultured ehrlich ascites tumor cells

Hauptlorenz, S.; Esterbauer, Hermann; Moll, Willi; Pümpel, Rolf; Schauenstein, E.; Puschendorf, Bernd

doi:10.1016/0006-2952(85)90428-9

Cited by 110 publications

(35 citation statements)

References 22 publications

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“…The interaction of HNE with proteins is complex because of the multiple reactive groups comprising the polar head of HNE, which allows for crosslinks between functional groups such as thiols, amino groups, and histidine residues. Structure-activity comparisons with compounds related to HNE have been used previously to assess the contribution of individual functional groups to the biological effects of HNE, with somewhat variable results, depending on the toxic endpoint examined (Hauptlorenz et al, 1985;Brambilla et al, 1986;Kaneko et al, 1988). Our present studies have focused on the structural contributions to induction of apoptosis compared with the effects of these structural determinants on survival and subsequent growth in a murine macrophage cell line.…”

Section: Discussionmentioning

confidence: 99%

Structure-Activity Relationships for Growth Inhibition and Induction of Apoptosis by 4-Hydroxy-2-nonenal in Raw 264.7 Cells

et al. 2000

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4-Hydroxy-2-nonenal (HNE) is a highly reactive lipid aldehyde byproduct of the peroxidation of cellular membranes. The structure of HNE features three functional groups, a C1 aldehyde, a C2AC3 double bond, and a C4-hydroxyl group, each of which may contribute to the toxicity of the compound. In addition, the length of the aliphatic chain may influence toxic potency by altering lipophilicity. Using analogous compounds that lacked one or more of the structural moieties, the role of each of these structural motifs in the cytotoxicity of HNE was examined in a mouse alveolar macrophage cell line (RAW 264.7) by a cell survival and growth assay. The importance of these functional groups in the potency of HNE for induction of apoptosis was also examined. The rank order of effects on toxicity was C1Oaldehyde Ն C2AC3 double bond Ͼ Ͼ C4Ohydroxyl, with parallel results in both the survival/growth inhibition and apoptosis induction assays. The chain length also influenced toxicity in a series of ␣,␤-unsaturated alkenyl aldehydes, with increasing chain length yielding increasing toxicity. To confirm the importance of the aldehyde moiety, and to examine the role of metabolic detoxification in cellular defenses against HNE toxicity, a RAW 264.7 cell line overexpressing human aldehyde dehydrogenase-3 (hALDH3) was generated. This cell line exhibited nearly complete protection against HNEprotein adduct formation as well as HNE-induced apoptosis. These results illustrate the comparative significance of key structural features of HNE in relation to its potent toxicity and induction of apoptosis.

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Section: Discussionmentioning

confidence: 99%

Structure-Activity Relationships for Growth Inhibition and Induction of Apoptosis by 4-Hydroxy-2-nonenal in Raw 264.7 Cells

et al. 2000

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“…HNE is a highly electrophilic agent which readily reacts with biomolecules containing sulphydryl (SH) groups including cysteine (Esterbauer et ai, 1976), glutathione (Esterbauer et ai, 1975) and SH proteins such as DNA polymerase (Hauptlorenz et al, 1985). HNE also reacts with amino groups in low-density lipoproteins (LDL) (Hoffe/ al, 1989) and deoxyguanosine (Winter et ai, 1986).…”

Section: Introductionmentioning

confidence: 99%

Content of significant amounts of a cytotoxic end-product of lipid peroxidation in human semen

Selley

Lacey²,

Bartlett³

et al. 1991

Reproduction

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Summary. (E)-4-Hydroxy-2-nonenal (HNE), a cytotoxic end-product of lipid peroxidation, is present in significant amounts in human semen (0\m=.\902\ m=+-\ 0\m=.\190\g=m\M; mean \ m= + -\ s.e.; n = 18). The addition of the divalent cation ionophore A23187 to suspensions of human spermatozoa resulted in increased production of HNE. Exogenous HNE was powerfully spermicidal and as little as 50\g=m\M caused an irreversible loss of motility of human spermatozoa within minutes. The addition of human seminal plasma protected spermatozoa from the toxic effects of HNE.

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“…Many anti-neoplastic agents have clearly established mechanisms of action that are not dependent upon the generation of ROS/RNS; however, these drugs can only mediate their anticancer effects on cancer cells that exhibit unrestricted progression through the cell cycle and have intact apoptotic pathways. Oxidative stress interferes with cell cycle progression by inhibiting the transition of cells from the G 0 to G 1 phase, slowing progression through S phase by inhibition of DNA synthesis, inhibiting cell cycle progression of G 1 to S phase, and by checkpoint arrest (Balin et al, 1978;Gonzalez, 1992;Hauptlorenz et al, 1985;Kurata, 2000;Schackelford et al, 2000). Chemotherapeutic agents can also activate DNA repair systems.…”

Section: Cancer Therapy Causes Excess Oxidative Stress and Severe Fatmentioning

confidence: 99%

Nutritional Supplements for Cancer-Associated

Nicolson¹

2012

Topics in Cancer Survivorship

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Effects of the lipidperoxidation product 4-hydroxynonenal and related aldehydes on proliferation and viability of cultured ehrlich ascites tumor cells

Cited by 110 publications

References 22 publications

Structure-Activity Relationships for Growth Inhibition and Induction of Apoptosis by 4-Hydroxy-2-nonenal in Raw 264.7 Cells

Structure-Activity Relationships for Growth Inhibition and Induction of Apoptosis by 4-Hydroxy-2-nonenal in Raw 264.7 Cells

Content of significant amounts of a cytotoxic end-product of lipid peroxidation in human semen

Nutritional Supplements for Cancer-Associated

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