Protein tyrosine phosphatase activities are involved in apoptotic cancer cell death induced by GL331, a new homolog of etoposide

Tze Sing Huang, Chih Hung Shu, Yung Luen Shih, Huey Chung Huang, Yi Chun Su, Yee Chao, Wen K. Yang, Jacqueline Whang-Peng

Research output: Contribution to journalArticlepeer-review

40 Citations (Scopus)

Abstract

GL331 is a semisynthetic topoisomerase II inhibitor derived from a plant toxin podophyllotoxin. In 72-h exposure assays, LD50 values of GL331 range from 0.5 to 2 μM, which are three- to ten-fold lower than those of its homologous compound etoposide (VP-16), depending on different cancer cell lines including nasopharyngeal, hepatocellular, gastric, cervical and colon cancer types. Apoptotic DNA ladders could be detected when cancer cells were treated with GL331 for 24 h even if the Bcl-2 and Bax protein levels were not altered during the period. Besides acting as topoisomerase II inhibitors, both GL331 and VP-16 decrease the cellular protein tyrosine kinase (PTK) activities in cancer cells. The activities of protein tyrosine phosphatase (PTP) are significantly increased after GL331 treatment but are not affected by VP-16. GL331-induced internucleosomal cleavage can be efficiently prevented by two inhibitors of PTP, sodium orthovanadate and zinc chloride, but not by okadaic acid, which inhibits serine/threonine phosphatase activity. These results indicate that GL331 may induce apoptotic cell death, and that activation of protein tyrosine phosphatases may be involved in this process.

Original languageEnglish
Pages (from-to)77-85
Number of pages9
JournalCancer Letters
Volume110
Issue number1-2
DOIs
Publication statusPublished - Dec 20 1996
Externally publishedYes

Keywords

  • Apoptosis
  • Etoposide (VP-16)
  • GL331
  • Protein tyrosine kinase
  • Protein tyrosine phosphatase

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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