pCramoll and rCramoll lectins induce cell death in human prostate adenocarcinoma (PC-3) cells by impairment of mitochondrial homeostasis

Toxicol In Vitro. 2017 Sep:43:40-46. doi: 10.1016/j.tiv.2017.05.016. Epub 2017 May 25.

Abstract

Lectins from Cratylia mollis seed have shown potential in vivo antitumor actions, however the mechanism have not yet been addressed. Here we evaluated the antitumor effects of native (pCramoll) and recombinant (rCramoll) lectins from C. mollis against human prostate adenocarcinoma (PC-3) cells. The viability of PC-3 cells was analyzed with the MTT assay and ANNEXIN V/propidium iodide staining. The actions of pCramoll or rCramoll on mitochondrial superoxide production, free cytosolic calcium concentration and mitochondrial membrane potential were evaluated using fluorescent probes (MitoSox Red, Fura 2-AM and safranin O, respectively). pCramoll and rCramoll reduced the viability of PC-3 cells in a dose-dependent manner. Both lectins increased the generation of mitochondrial superoxide as well as the concentration of cytosolic calcium. These changes led to a decrease in oxidative phosphorylation, which impaired the formation of ATP. The resulting cell death was not blocked by MPT (mitochondrial permeability transition) inhibitors (Debio 025 or bongkrekic acid). Thus pCramoll and rCramoll promote PC-3 cell death through calcium signaling, leading to mitochondrial collapse. This work provides more insights into the action of pCramoll and rCramoll against cancer cells. These lectins represent valuable tools for biomedical research.

Keywords: Cell death; Cytosolic calcium; Mitochondrial dysfunction; Oxidative stress; Plant lectin.

MeSH terms

  • Adenocarcinoma / drug therapy
  • Adenocarcinoma / metabolism
  • Antineoplastic Agents / pharmacology*
  • Calcium / metabolism
  • Cell Death / drug effects
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Fabaceae*
  • Homeostasis / drug effects
  • Humans
  • Male
  • Membrane Potential, Mitochondrial / drug effects
  • Mitochondria / drug effects
  • Mitochondria / metabolism
  • Mitochondria / physiology
  • Oxidative Phosphorylation / drug effects
  • Plant Lectins / pharmacology*
  • Prostatic Neoplasms / drug therapy
  • Prostatic Neoplasms / metabolism
  • Recombinant Proteins / pharmacology
  • Seeds
  • Superoxides / metabolism

Substances

  • Antineoplastic Agents
  • Plant Lectins
  • Recombinant Proteins
  • Superoxides
  • Calcium