Sulforaphane attenuates EGFR signaling in NSCLC cells

J Biomed Sci. 2015 Jun 3;22(1):38. doi: 10.1186/s12929-015-0139-x.

Abstract

Background: EGFR, a receptor tyrosine kinase (RTK), is frequently overexpressed and mutated in non-small cell lung cancer (NSCLC). Tyrosine kinase inhibitors (TKIs) have been widely used in the treatment of many cancers, including NSCLC. However, intrinsic and acquired resistance to TKI remains a common obstacle. One strategy that may help overcome EGFR-TKI resistance is to target EGFR for degradation. As EGFR is a client protein of heat-shock protein 90 (HSP90) and sulforaphane is known to functionally regulate HSP90, we hypothesized that sulforaphane could attenuate EGFR-related signaling and potentially be used to treat NSCLC.

Results: Our study revealed that sulforaphane displayed antitumor activity against NSCLC cells both in vitro and in vivo. The sensitivity of NSCLC cells to sulforaphane appeared to positively correlate with the inhibition of EGFR-related signaling, which was attributed to the increased proteasomal degradation of EGFR. Combined treatment of NSCLC cells with sulforaphane plus another HSP90 inhibitor (17-AAG) enhanced the inhibition of EGFR-related signaling both in vitro and in vivo.

Conclusions: We have shown that sulforaphane is a novel inhibitory modulator of EGFR expression and is effective in inhibiting the tumor growth of EGFR-TKI-resistant NSCLC cells. Our findings suggest that sulforaphane should be further explored for its potential clinical applications against NSCLC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology*
  • Carcinoma, Non-Small-Cell Lung / physiopathology
  • Cell Line, Tumor
  • ErbB Receptors / genetics*
  • ErbB Receptors / metabolism
  • Humans
  • Isothiocyanates / pharmacology*
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Random Allocation
  • Signal Transduction / drug effects*
  • Sulfoxides

Substances

  • Antineoplastic Agents
  • Isothiocyanates
  • Sulfoxides
  • EGFR protein, human
  • ErbB Receptors
  • sulforaphane