title: Chemotherapy Agents Alter Plasma Lipids in Breast Cancer Patients and Show Differential Effects on Lipid Metabolism Genes in Liver Cells.
abstract: Cardiovascular complications have emerged as a major concern for cancer patients. Many chemotherapy agents are cardiotoxic and some appear to also alter lipid profiles, although the mechanism for this is unknown. We studied plasma lipid levels in 12 breast cancer patients throughout their chemotherapy. Patients received either four cycles of doxorubicin and cyclophosphamide followed by weekly paclitaxel or three cycles of epirubicin, cyclophosphamide and 5'-fluorouracil followed by three cycles of docetaxel. Patients demonstrated a significant reduction (0.32 mmol/L) in high density lipoprotein cholesterol (HDL-C) and apolipoprotein A1 (apoA1) levels (0.18 g/L) and an elevation in apolipoprotein B (apoB) levels (0.15 g/L) after treatment. Investigation of the individual chemotherapy agents for their effect on genes involved in lipoprotein metabolism in liver cells showed that doxorubicin decreased ATP binding cassette transporter A1 (ABCA1) via a downregulation of the peroxisomal proliferator activated receptor γ (PPARγ) and liver X receptor α (LXRα) transcription factors. In contrast, ABCA1 levels were not affected by cyclophosphamide or paclitaxel. Likewise, apoA1 levels were reduced by doxorubicin and remained unaffected by cyclophosphamide and paclitaxel. Doxorubicin and paclitaxel both increased apoB protein levels and paclitaxel also decreased low density lipoprotein receptor (LDLR) protein levels. These findings correlate with the observed reduction in HDL-C and apoA1 and increase in apoB levels seen in these patients. The unfavourable lipid profiles produced by some chemotherapy agents may be detrimental in the longer term to cancer patients, especially those already at risk of cardiovascular disease (CVD). This knowledge may be useful in tailoring effective follow-up care plans for cancer survivors.
authors.affiliation: Department of Biochemistry, University of Otago, Dunedin, New Zealand.
authors.forename: Monika
authors.initials: M
authors.lastname: Sharma
authors.affiliation: Southern Blood and Cancer Service, Dunedin Hospital, Dunedin, New Zealand.
authors.forename: Jo
authors.initials: J
authors.lastname: Tuaine
authors.affiliation: Southern Blood and Cancer Service, Dunedin Hospital, Dunedin, New Zealand.
authors.forename: Blair
authors.initials: B
authors.lastname: McLaren
authors.affiliation: Department of Medicine, University of Otago, Dunedin, New Zealand.
authors.forename: Debra L
authors.initials: DL
authors.lastname: Waters
authors.affiliation: Department of Human Nutrition, University of Otago, Dunedin, New Zealand.
authors.forename: Katherine
authors.initials: K
authors.lastname: Black
authors.affiliation: School of Physical Education, Sport and Exercise Sciences, University of Otago, Dunedin, New Zealand.
authors.forename: Lynnette M
authors.initials: LM
authors.lastname: Jones
authors.affiliation: Department of Biochemistry, University of Otago, Dunedin, New Zealand.
authors.forename: Sally P A
authors.initials: SP
authors.lastname: McCormick
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000097:blood / Q000378:metabolism; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D016632:Apolipoprotein A-I / Q000097:blood / Q000378:metabolism; D001055:Apolipoproteins B / Q000097:blood / Q000378:metabolism; D001943:Breast Neoplasms / Q000097:blood / Q000378:metabolism; D008076:Cholesterol, HDL / Q000097:blood; D003520:Cyclophosphamide / Q000009:adverse effects / Q000627:therapeutic use; D004317:Doxorubicin / Q000009:adverse effects / Q000627:therapeutic use; D015251:Epirubicin / Q000009:adverse effects / Q000627:therapeutic use; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D050356:Lipid Metabolism / Q000187:drug effects* / Q000235:genetics*; D008055:Lipids / Q000097:blood*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism*; D008875:Middle Aged; D047495:PPAR gamma / Q000097:blood / Q000378:metabolism
chemical_list: C505693:APOA1 protein, human; D018528:ATP-Binding Cassette Transporters; D000970:Antineoplastic Agents; D016632:Apolipoprotein A-I; D001055:Apolipoproteins B; D008076:Cholesterol, HDL; D008055:Lipids; D047495:PPAR gamma; D015251:Epirubicin; D004317:Doxorubicin; D003520:Cyclophosphamide