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

43 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

Fingerprint

Phellinus linteus
Urinary Bladder Neoplasms
breast neoplasms
Cells
Breast Neoplasms
neoplasms
caspase-7
Phellinus
proto-oncogenes
stomach neoplasms
cyclin-dependent kinase
cells
carcinogenesis
Tumors
cell growth
apoptosis
therapeutics
Down-Regulation
Caspase 7
urinary bladder neoplasms

Keywords

  • Hispolon
  • MDM2
  • p21
  • p53
  • Ubiquitination

ASJC Scopus subject areas

  • Food Science
  • Toxicology

Cite this

Hispolon from Phellinus linteus has antiproliferative effects via MDM2-recruited ERK1/2 activity in breast and bladder cancer cells. / Lu, Te Ling; Huang, Guan Jhong; Lu, Te Jung; Wu, Jin Bin; Wu, Chieh Hsi; Yang, Tung Chuan; Iizuka, Akira; Chen, Yuh Fung.

In: Food and Chemical Toxicology, Vol. 47, No. 8, 08.2009, p. 2013-2021.

Research output: Contribution to journalArticle

Lu, Te Ling ; Huang, Guan Jhong ; Lu, Te Jung ; Wu, Jin Bin ; Wu, Chieh Hsi ; Yang, Tung Chuan ; Iizuka, Akira ; Chen, Yuh Fung. / Hispolon from Phellinus linteus has antiproliferative effects via MDM2-recruited ERK1/2 activity in breast and bladder cancer cells. In: Food and Chemical Toxicology. 2009 ; Vol. 47, No. 8. pp. 2013-2021.
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