Intervention of transplantable human mammary carcinoma MX-1 chemotherapy with dietary menhaden oil in athymic mice: increased therapeutic effects and decreased toxicity of cyclophosphamide.
We investigated the effects of dietary menhaden oil on cyclophosphamide (CP) antineoplastic activity and its protective effect against CP toxicity. We found that dietary menhaden oil (HMO, 20% menhaden oil + 5% corn oil) enhanced the CP antitumor effect at the lowest dose tested (50 mg/kg) compared with the control group (LCO, 5% corn oil). Dietary HMO and CP treatment had a significant effect on the activities of tumor and liver microsomal cytochrome P-450 (CYP) over the controls. Activity of one of the key CP activating enzymes, CYP2B1 (which is similar to human CYP2B6), was significantly enhanced in the liver and tumor by the HMO diet, which could result in the formation of more pharmacologically active CP metabolites and, therefore, increased CP antitumor response. Moreover, the HMO diet exhibited a very significant protective effect against CP acute toxicity. The activity of the CP detoxifying enzyme aldehyde dehydrogenase (ADH) was significantly increased in the liver after HMO feeding; thus the observed protective effect of HMO feeding against CP toxicity may be partially the result of induction of ADH activity in the liver. In summary, our findings suggested that dietary menhaden oil can modulate ADH and CYP activities in a manner that may alter the metabolism of CP and, therefore, improve its therapeutic index by increasing its therapeutic effect and decreasing its toxicity.
Shao
Y
Y
Allie M. Lee Laboratory for Cancer Research, Department of Biochemistry, University of Nevada, Reno 89557, USA.
Pardini
L
L
Pardini
R S
RS
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002455:Cell Division; D003520:Cyclophosphamide / Q000627:therapeutic use* / Q000633:toxicity*; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004042:Dietary Fats, Unsaturated / Q000008:administration & dosage / Q000627:therapeutic use*; D005260:Female; D005395:Fish Oils / Q000008:administration & dosage / Q000627:therapeutic use*; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008861:Microsomes / Q000378:metabolism; D008862:Microsomes, Liver / Q000201:enzymology; D009368:Neoplasm Transplantation; D013739:Testosterone / Q000378:metabolism
D000970:Antineoplastic Agents; D004042:Dietary Fats, Unsaturated; D005395:Fish Oils; D007527:Isoenzymes; C033266:Menhaden oil; D013739:Testosterone; D003520:Cyclophosphamide; D003577:Cytochrome P-450 Enzyme System