Hispolon from Phellinus linteus has antiproliferative effects via MDM2-recruited ERK1/2 activity in breast and bladder cancer cells

Te Ling Lu, Guan Jhong Huang, Te Jung Lu, Jin Bin Wu, Chieh Hsi Wu, Tung Chuan Yang, Akira Iizuka, Yuh Fung Chen

Research output: Contribution to journalArticle

48 Citations (Scopus)

Abstract

The MDM2 proto-oncogene is overexpressed in many human tumors. Although MDM2 inhibits tumor-suppressor function of p53, there exists a p53-independent role for MDM2 in tumorigenesis. Therefore, downregulation of MDM2 has been considered an attractive therapeutic strategy. Hispolon extracted from Phellinus species was found to induce epidermoid and gastric cancer cell apoptosis. However, the mechanisms are not fully understood. Herein, we report our findings that hispolon inhibited breast and bladder cancer cell growth, regardless of p53 status. Furthermore, p21 WAF1, a cyclin-dependent kinase inhibitor, was elevated in hispolon-treated cells. MDM2, a negative regulator of p21 WAF1, was ubiquitinated and degraded after hispolon treatment. We also found that activated ERK1/2 (extracellular signal-regulated kinase1/2) was recruited to MDM2 and involved in mediating MDM2 ubiquitination. Based on this finding, we investigated whether the sensitivity of cells to hispolon was related to ERK1/2 activity. The results indicated that cells with higher ERK1/2 activity were more sensitive to hispolon. In addition, hispolon-induced caspase-7 cleavage was inhibited by the ERK1/2 inhibitor, U0126. In conclusion, hispolon ubiquitinates and downregulates MDM2 via MDM2-recruited activated ERK1/2. Therefore, hispolon may be a potential anti-tumor agent in breast and bladder cancers.

Original languageEnglish
Pages (from-to)2013-2021
Number of pages9
JournalFood and Chemical Toxicology
Volume47
Issue number8
DOIs
Publication statusPublished - Aug 2009
Externally publishedYes

Keywords

  • Hispolon
  • MDM2
  • p21
  • p53
  • Ubiquitination

ASJC Scopus subject areas

  • Food Science
  • Toxicology

Fingerprint Dive into the research topics of 'Hispolon from Phellinus linteus has antiproliferative effects via MDM2-recruited ERK1/2 activity in breast and bladder cancer cells'. Together they form a unique fingerprint.

  • Cite this