TMPyP4 promotes cancer cell migration at low doses, but induces cell death at high doses

Sci Rep. 2016 May 25:6:26592. doi: 10.1038/srep26592.

Abstract

TMPyP4 is widely considered as a potential photosensitizer in photodynamic therapy and a G-quadruplex stabilizer for telomerase-based cancer therapeutics. However, its biological effects including a possible adverse-effect are poorly understood. In this study, whole genome RNA-seq analysis was used to explore the alteration in gene expression induced by TMPyP4. Unexpectedly, we find that 27.67% of changed genes were functionally related to cell adhesion. Experimental evidences from cell adhesion assay, scratch-wound and transwell assay indicate that TMPyP4 at conventional doses (≤0.5 μM) increases cell-matrix adhesion and promotes the migration of tumor cells. In contrast, a high dose of TMPyP4 (≥2 μM) inhibits cell proliferation and induces cell death. The unintended "side-effect" of TMPyP4 on promoting cell migration suggests that a relative high dose of TMPyP4 is preferred for therapeutic purpose. These findings contribute to better understanding of biological effects induced by TMPyP4 and provide a new insight into the complexity and implication for TMPyP4 based cancer therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • A549 Cells
  • Cell Death / drug effects
  • Cell Movement / drug effects*
  • Cell Proliferation / drug effects*
  • Dose-Response Relationship, Drug
  • HeLa Cells
  • Humans
  • Neoplasms / genetics
  • Neoplasms / metabolism*
  • Neoplasms / pathology
  • Porphyrins / pharmacology*

Substances

  • Porphyrins
  • tetra(4-N-methylpyridyl)porphine