In vivo tumor growth inhibition by Solanum tuberosum aspartic protease 3 (StAP3) treatment

Bioorg Med Chem Lett. 2021 Jun 1:41:127959. doi: 10.1016/j.bmcl.2021.127959. Epub 2021 Mar 22.

Abstract

Solanum tuberosum aspartic Proteases (StAPs) show selective plasma membrane permeabilization, inducing cytotoxicity of cancer cells versus normal cells in vitro. Herein, we aimed to evaluate both StAP3 systemic toxicity and antitumoral activity against human melanoma in vivo. The toxicity of a single high dose of StAP3 (10 µg/g body weight, intraperitoneally) was assessed in a Balb/c mice model. Subcutaneous A375 human melanoma xenografts in athymic nude (nu/nu) mice were induced. Once tumors developed (mean larger dimension = 3.8 ± 0.09 mm), mice were StAP3-treated (6 µg/g body weight, subcutaneously under the tumor at a single dose). For both models, controls were treated with physiologic saline solution. StAP3-treated mice showed a significant inhibition of tumor growth (p < 0.05) compared with controls. No signs of toxicity were detected in StAP3-treated mice in both models. These results suggest the potential of these plant proteases as anticancer agents.

Keywords: Cancer; Melanoma; Plasma membrane interaction; Potato; Saposin-like domain (PSI).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents, Phytogenic / metabolism
  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Aspartic Acid Proteases / metabolism
  • Aspartic Acid Proteases / pharmacology*
  • Cell Line, Tumor
  • Humans
  • Melanoma / drug therapy*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Neoplasms, Experimental / drug therapy
  • Plant Proteins / genetics
  • Plant Proteins / metabolism
  • Plant Proteins / pharmacology
  • Solanum tuberosum / enzymology*

Substances

  • Antineoplastic Agents, Phytogenic
  • Plant Proteins
  • Aspartic Acid Proteases