Lipids

, 30:1035

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

  • Yu Shao
  • Lani Pardini
  • Ronald S. Pardini
Article

DOI: 10.1007/BF02536289

Cite this article as:
Shao, Y., Pardini, L. & Pardini, R.S. Lipids (1995) 30: 1035. doi:10.1007/BF02536289

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.

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

Copyright information

© American Oil Chemists’ Society 1995

Authors and Affiliations

  • Yu Shao
    • 1
  • Lani Pardini
    • 1
  • Ronald S. Pardini
    • 1
  1. 1.Allie M. Lee Laboratory for Cancer Research, Department of BiochemistryUniversity of NevadaReno