Bauhinia variegata candida Fraction Induces Tumor Cell Death by Activation of Caspase-3, RIP, and TNF-R1 and Inhibits Cell Migration and Invasion In Vitro

Biomed Res Int. 2018 Mar 25;2018:4702481. doi: 10.1155/2018/4702481. eCollection 2018.

Abstract

Metastasis remains the most common cause of death in cancer patients. Inhibition of metalloproteinases (MMPs) is an interesting approach to cancer therapy because of their role in the degradation of extracellular matrix (ECM), cell-cell, and cell-ECM interactions, modulating key events in cell migration and invasion. Herein, we show the cytotoxic and antimetastatic effects of the third fraction (FR3) from Bauhinia variegata candida (Bvc) stem on human cervical tumor cells (HeLa) and human peripheral blood mononuclear cells (PBMCs). FR3 inhibited MMP-2 and MMP-9 activity, indicated by zymogram. This fraction was cytotoxic to HeLa cells and noncytotoxic to PBMCs and decreased HeLa cell migration and invasion. FR3 is believed to stimulate extrinsic apoptosis together with necroptosis, assessed by western blotting. FR3 inhibited MMP-2 activity in the HeLa supernatant, differently from the control. The atomic mass spectrometry (ESI-MS) characterization suggested the presence of glucopyranosides, D-pinitol, fatty acids, and phenolic acid. These findings provide insight suggesting that FR3 contains components with potential tumor-selective cytotoxic action in addition to the action on the migration of tumor cells, which may be due to inhibition of MMPs.

MeSH terms

  • Apoptosis / drug effects
  • Bauhinia / chemistry*
  • Caspase 3 / metabolism*
  • Cell Death / drug effects*
  • Cell Line, Tumor
  • Cell Movement / drug effects*
  • Cytotoxins / pharmacology
  • Fatty Acids / pharmacology
  • HeLa Cells
  • Humans
  • Hydroxybenzoates / pharmacology
  • Inositol / analogs & derivatives
  • Inositol / pharmacology
  • Leukocytes, Mononuclear / drug effects
  • Matrix Metalloproteinase 2 / metabolism
  • Matrix Metalloproteinase 9 / metabolism
  • Neoplasm Invasiveness / prevention & control
  • Plant Extracts / pharmacology*
  • Receptor-Interacting Protein Serine-Threonine Kinases / metabolism*
  • Receptors, Tumor Necrosis Factor, Type I / metabolism*
  • Signal Transduction / drug effects

Substances

  • Cytotoxins
  • Fatty Acids
  • Hydroxybenzoates
  • Plant Extracts
  • Receptors, Tumor Necrosis Factor, Type I
  • pinitol
  • Inositol
  • Receptor-Interacting Protein Serine-Threonine Kinases
  • CASP3 protein, human
  • Caspase 3
  • Matrix Metalloproteinase 2
  • Matrix Metalloproteinase 9
  • phenolic acid