Apolipoprotein mimetics in cancer
Por:
Delk, SC, Chattopadhyay, A, Escola-Gil, JC, Fogelman, AM, Reddy, ST
Publicada:
1 ago 2021
Ahead of Print:
1 jun 2021
Resumen:
Peptides have many advantages over traditional therapeutics, including small molecules and other biologics, because of their low toxicity and immunogenicity, while still exhibiting efficacy. This review discusses the benefits and mechanism of action of apolipoprotein mimetic peptides in tumor biology and their potential utility in treating various cancers. Among lipoproteins in the circulation, high-density lipoprotein (HDL) and its constituents including apolipoprotein A-I (apoA-I; the predominant protein in HDL), apoJ, and apoE, harbor antitumorigenic activities. Peptides that mimic apoA-I function have been developed through molecular mimicry of the amphipathic alpha-helices of apoA-I. Oral apoA-I mimetic peptides remodel HDL, promote cholesterol efflux, sequester oxidized lipids, and activate anti-inflammatory processes. ApoA-I and apoJ mimetic peptides ameliorate various metrics of cancer progression and have demonstrated efficacy in preclinical models in the inhibition of ovarian, colon, breast, and metastatic lung cancers. Apolipoprotein mimetic peptides are poorly absorbed when administered orally and rapidly degraded when injected into the circulation. The small intestine is the major site of action for apoA-I mimetic peptides and recent studies suggest that modulation of immune cells in the lamina propria of the small intestine is, in part, a potential mechanism of action. Finally, several recent studies underscore the use of reconstituted HDL as target-specific nanoparticles carrying poorly soluble or unstable therapeutics to tumors even across the blood-brain barrier. Preclinical studies suggest that these versatile recombinant lipoprotein based nanoparticles and apolipoprotein mimetics can serve as safe, novel drug delivery, and therapeutic agents for the treatment of a number of cancers.
Filiaciones:
Delk, SC:
Univ Calif Los Angeles, Fielding Sch Publ Hlth, Mol Toxicol Interdepartmental Degree Program, Los Angeles, CA 90095 USA
UCLA, David Geffen Sch Med, Div Cardiol, Dept Med, Los Angeles, CA 90095 USA
Chattopadhyay, A:
UCLA, David Geffen Sch Med, Div Cardiol, Dept Med, Los Angeles, CA 90095 USA
Escola-Gil, JC:
Inst Invest Biomed IIB St Pau, St Quinti 77, Barcelona 08041, Spain
CIBER Diabet & Enfermedades Metab Asociadas CIBER, Monforte Lemos 3-5, Madrid 28029, Spain
Univ Autonoma Barcelona, Dept Bioquim & Biol Mol, Antoni M Claret 167, Barcelona 08025, Spain
Fogelman, AM:
UCLA, David Geffen Sch Med, Div Cardiol, Dept Med, Los Angeles, CA 90095 USA
Reddy, ST:
Univ Calif Los Angeles, Fielding Sch Publ Hlth, Mol Toxicol Interdepartmental Degree Program, Los Angeles, CA 90095 USA
UCLA, David Geffen Sch Med, Div Cardiol, Dept Med, Los Angeles, CA 90095 USA
UCLA, David Geffen Sch Med, Mol & Med Pharmacol, Los Angeles, CA 90095 USA
UCLA, David Geffen Sch Med, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90095 USA
Green Accepted
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