Abstract
Novel therapeutic approaches, free of secondary side effects, are desperately needed for the treatment of cancers especially recurrent, chemotherapy-resistant cancers. It is now established that inflammation and lipoprotein metabolism play an important role in cancer development and progression. The serendipitous discovery that plasma/serum levels of HDL-associated proteins, apolipoprotein A-I (ApoA-I), transthyretin, and transferrin, are markers for the detection of early-stage ovarian cancer led to the hypothesis that HDL may play a critical role in the development and progression of cancer. Studies in mouse models established that apoA-I has antitumorigenic properties. ApoA-I mimetic peptides administered orally or subcutaneously reduce tumor growth and tumor burden in mouse models of ovarian cancer and colon cancer by suppressing angiogenesis and proliferation. Antioxidant, lipid-binding, and anti-inflammatory properties of apoA-I mimetic peptides appear to be their primary mechanism of action. In vivo and in vitro studies implicate multiple pathways including VEGF, MnSOD, and HIF1-α in mediating the antiangiogenic and antiproliferative properties of apoA-I mimetic peptides. The antiproliferative effects of apoA-I mimetic peptides on the viability of human papillary serous adenocarcinoma cell lines resistant to cis-platinum suggest that apoA-I mimetic peptides may be efficacious for the treatment of at least some of the chemotherapy-resistant types of cancer.
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Acknowledgments
This work was supported in part by US Public Health Service Research Grants HL-30568, a Network grant from the Leducq Foundation, the Laubisch, Castera, and M.K. Grey Funds at UCLA, the Women’s Endowment, the Carl and Roberta Deutsch Family Foundation, the Joan English Fund for Women’s Cancer Research, Kelly Day, the OVARIAN CANCER Coalition, the Helen Beller Foundation, Wendy Stark Foundation, and Sue and Mel Geliebter Family Foundation.
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M.N., S.T.R, G.M.A, and A.M.F. are principals in Bruin Pharma, and A.M.F. is an officer in Bruin Pharma.
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Farias-Eisner, R., Su, F., Anantharamahiah, G.M., Navab, M., Fogelman, A.M., Reddy, S.T. (2015). Apolipoprotein A-I Mimetic Peptides in Mouse Models of Cancer. In: Anantharamaiah, G., Goldberg, D. (eds) Apolipoprotein Mimetics in the Management of Human Disease. Adis, Cham. https://doi.org/10.1007/978-3-319-17350-4_5
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DOI: https://doi.org/10.1007/978-3-319-17350-4_5
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