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Dietary menhaden oil enhances mitomycin C antitumor activity toward human mammary carcinoma MX-1

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Lipids

Abstract

In the present study, we investigated the effects of high levels of dietary fish oil on the growth of MX-1 human mammary carcinoma and its response to mitomycin C (MC) treatment in athymic mice. We found that high levels of dietary fish oil (20% menhaden oil+5% corn oil, w/w) compared to a control diet (5% corn oil, w/w) not only lowered the tumor growth rate, but also increased the tumor response to MC treatment. We also found that high levels of dietary fish oil significantly increased the activities of tumor xanthine oxidase and DT-diaphorase, which are proposed to be involved in the bioreductive activation of MC. Since menhaden oil is highly unsaturated, its intake caused a significant increase in the degree of fatty acid unsaturation in tumor membrane phospholipids. This alteration in tumor membrane phospholipids made the tumor more susceptible to oxidative stress, as indicated by the increased levels of both endogenous lipid peroxidation and protein oxidation after feeding the host animals the menhaden oil diet. In addition, the tumor antioxidant enzyme activities, catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPOx), and glutathione S-transferase peroxidase (GSTPx), were all significantly enhanced by feeding a diet high in fish oil. MC treatment caused further increases in tumor lipid peroxidation and protein oxidation, as well as in the activities of CAT, SOD, GPOx, and GSTPx, suggesting that MC causes oxidative stress in this tumor model which is exacerbated by feeding a diet high in menhaden oil. Thus, feeding a diet rich in menhaden oil decreased the growth of human mammary carcinoma MX-1, increased its responsiveness to MC, and increased its susceptibility to endogenous and MC-induced oxidative stress, and increased the tumor activities of two enzymes proposed to be involved in the bioactivation of MC, that is, DT-diaphorase and xanthine oxidase. These findings support a role of these two enzymes in the bioactivating of MC and indicate that the type of dietary fat may be important in tumor response to therapy.

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Abbreviations

CAT:

catalase

CB5R:

cytochrome b5 reductase

CCR:

cytochrome C reductase

CO:

corn oil

DHA:

docosahexaenoic acid

DNPH:

3,4-dinitrophenyl hydrazine

DTD:

DT-diaphorase

EPA:

eicosapentaenoic acid

GPOx:

glutathione peroxidase

GR:

glutathione reductase

GSH:

glutathione

GSSG:

glutathione disulfide

GST:

glutathione S-transferase

GSTPx:

glutathione S-transferase peroxidase

HNE:

4-hydroxy-nonenal

MC:

mitomycin C

MO:

menhaden oil

PL:

phospholipid

PUFAs:

polyunsaturated fatty acids

SOD:

superoxide dismutase

TBARS:

thiobarbituric reactive substances

T/C:

treat/control ratio

XD:

xanthine dehydrogenase

XO:

xanthine oxidase

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Authors and Affiliations

  1. Allie M. Lee Laboratory for Cancer Research, Department of Biochemistry, University of Nevada, Mail Stop 330, 89557, Reno, Nevada

    Yu Shao, Lani Pardini & Ronald S. Pardini

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  1. Yu Shao
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  2. Lani Pardini
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  3. Ronald S. Pardini
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Shao, Y., Pardini, L. & Pardini, R.S. Dietary menhaden oil enhances mitomycin C antitumor activity toward human mammary carcinoma MX-1. Lipids 30, 1035–1045 (1995). https://doi.org/10.1007/BF02536289

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  • DOI: https://doi.org/10.1007/BF02536289

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