Antibody against N-terminal domain of phospholipid scramblase 1 induces apoptosis in colorectal cancer cells through the intrinsic apoptotic pathway

Chem Biol Drug Des. 2014 Jul;84(1):36-43. doi: 10.1111/cbdd.12347. Epub 2014 Jun 7.

Abstract

Phospholipid scramblase 1 involve in biological processes including phospholipid movement, proliferation, and apoptosis. Treatment with an antiphospholipid scramblase 1 antibody (NP1) has been demonstrated to inhibit cell proliferation in colorectal cancer. This study aimed to explore the role of NP1 treatment in the apoptosis of colorectal cancer cells. Results showed that NP1 treatment significantly increases the apoptosis of colorectal cancer cells via the activation of caspase 8, caspase 9, and caspase 3. Moreover, pretreatment with a caspase 8 inhibitor did not fully prevent the apoptotic effects of NP1. Taken together, these data indicate NP1 induces cell apoptosis primary through the intrinsic apoptotic pathway. NP1 may serve as a potential therapeutic agent.

Keywords: apoptosis; caspase; colorectal cancer; phospholipid scramblase 1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies / pharmacology*
  • Apoptosis / drug effects*
  • Caspase 3 / metabolism
  • Caspase 8 / metabolism
  • Caspase 9 / metabolism
  • Cell Line, Tumor
  • Colon / drug effects
  • Colon / enzymology
  • Colon / pathology
  • Colorectal Neoplasms / drug therapy*
  • Colorectal Neoplasms / enzymology*
  • Colorectal Neoplasms / pathology
  • Humans
  • Molecular Targeted Therapy*
  • Phospholipid Transfer Proteins / chemistry
  • Phospholipid Transfer Proteins / metabolism*
  • Protein Structure, Tertiary / drug effects
  • Rectum / drug effects
  • Rectum / enzymology
  • Rectum / pathology

Substances

  • Antibodies
  • PLSCR1 protein, human
  • Phospholipid Transfer Proteins
  • Caspase 3
  • Caspase 8
  • Caspase 9