Prostate tumor attenuation in the nu/nu murine model due to anti-sarcosine antibodies in folate-targeted liposomes

Sci Rep. 2016 Sep 20:6:33379. doi: 10.1038/srep33379.

Abstract

Herein, we describe the preparation of liposomes with folate-targeting properties for the encapsulation of anti-sarcosine antibodies (antisarAbs@LIP) and sarcosine (sar@LIP). The competitive inhibitory effects of exogenously added folic acid supported the role of folate targeting in liposome internalization. We examined the effects of repeated administration on mice PC-3 xenografts. Sar@LIP treatment significantly increased tumor volume and weight compared to controls treated with empty liposomes. Moreover, antisarAbs@LIP administration exhibited a mild antitumor effect. We also identified differences in gene expression patterns post-treatment. Furthermore, Sar@LIP treatment resulted in decreased amounts of tumor zinc ions and total metallothioneins. Examination of the spatial distribution across the tumor sections revealed a sarcosine-related decline of the MT1X isoform within the marginal regions but an elevation after antisarAbs@LIP administration. Our exploratory results demonstrate the importance of sarcosine as an oncometabolite in PCa. Moreover, we have shown that sarcosine can be a potential target for anticancer strategies in management of PCa.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal / administration & dosage*
  • Cell Line, Tumor
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Folic Acid / metabolism*
  • Humans
  • Liposomes* / chemistry
  • Liposomes* / ultrastructure
  • Male
  • Metallothionein / metabolism
  • Mice
  • Models, Biological
  • Phosphatidylethanolamines
  • Prostatic Neoplasms / drug therapy
  • Prostatic Neoplasms / metabolism*
  • Prostatic Neoplasms / pathology*
  • Sarcosine / antagonists & inhibitors*
  • Sarcosine / chemistry
  • Tumor Burden / drug effects
  • Xenograft Model Antitumor Assays
  • Zinc / metabolism

Substances

  • Antibodies, Monoclonal
  • Liposomes
  • Phosphatidylethanolamines
  • dioleoyl phosphatidylethanolamine
  • Metallothionein
  • Folic Acid
  • Zinc
  • Sarcosine