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Concomitant use of astaxanthin during doxorubicin chemotherapy against mammary cancer

Posted on:2007-04-27Degree:Ph.DType:Dissertation
University:Washington State UniversityCandidate:Nakao, RurikoFull Text:PDF
GTID:1444390005970484Subject:Health Sciences
Abstract/Summary:
Astaxanthin is a naturally occurring antioxidant that provides health benefits such as immunomodulation, anti-inflammation, cardioprotection and cancer prevention. The overall objective of this study was to evaluate the concomitant supplementation of astaxanthin during doxorubicin (DOX) chemotherapy on mammary tumor growth, immune response, inflammation and cardioprotection. In experiment 1, female BALB/c mice were fed a diet containing 0, 0.02, or 0.08% astaxanthin for 8 weeks. On week 2, mice were injected or not injected with DOX (1 mg/kg BW/week) weekly for 6 weeks. One week after the last DOX injection, echocardiography was performed and mice then were euthanized to obtain blood and tissues. The major astaxanthin isomer in the plasma of astaxanthin-fed mice was 13-cis astaxanthin, followed by the all-trans and 9-cis isomers. In mice not given DOX, 0.08% astaxanthin increased (P<0.05) heart contractility and mitochondrial membrane potential compared to mice fed the control diet. Experiment 2 was designed to study the timing of astaxanthin supplementation related to DOX chemotherapy on the inhibition of mammary tumor growth. Female BALB/c mice were assigned to the following treatments: control diet without DOX (2 mg/kg BW/week; C-DOX), control diet with DOX (C+DOX), 0.005% astaxanthin diet with DOX (A+DOX), and control diet on weeks -1 through 5 and then switched to the astaxanthin diet (CA+DOX). All mice were injected with 5x10 5 -SA mammary tumor cells into the mammary fat pad on week 0 and tumor growth measured daily. On week 8 after tumor challenge, echocardiography was performed. Mice were then killed to obtain blood and tissues. Tumor latency was delayed (P<0.05) by DOX and astaxanthin. In group A+DOX, tumor volume was consistently lower (P<0.05) than the other three groups throughout the study. When the diet was switched from control to astaxanthin in group CA+DOX, tumor volume increased (P<0.05) more rapidly than the other groups. Mice in group A+DOX but not in group CA+DOX had higher (P<0.05) NK cell population and plasma IFN-γ concentration compared to group C+DOX. Therefore, our data suggest that supplementation with astaxanthin prior to DOX chemotherapy may be beneficial in terms of delaying tumor growth and modulating immune response.
Keywords/Search Tags:DOX, Astaxanthin, Chemotherapy, Tumor, Mammary, Mice, Control diet
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