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 journalArticle

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

Fingerprint

Protein Tyrosine Phosphatases
Etoposide
Cell Death
Neoplasms
Topoisomerase II Inhibitors
Nasopharyngeal Neoplasms
Podophyllotoxin
bcl-2-Associated X Protein
Okadaic Acid
Vanadates
Phosphoprotein Phosphatases
Lethal Dose 50
Liver Neoplasms
GL 331
Sodium Chloride
Uterine Cervical Neoplasms
Protein-Tyrosine Kinases
Colonic Neoplasms
Stomach Neoplasms
Cell Line

Keywords

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

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Protein tyrosine phosphatase activities are involved in apoptotic cancer cell death induced by GL331, a new homolog of etoposide. / Huang, Tze Sing; Shu, Chih Hung; Shih, Yung Luen; Huang, Huey Chung; Su, Yi Chun; Chao, Yee; Yang, Wen K.; Whang-Peng, Jacqueline.

In: Cancer Letters, Vol. 110, No. 1-2, 20.12.1996, p. 77-85.

Research output: Contribution to journalArticle

Huang, Tze Sing ; Shu, Chih Hung ; Shih, Yung Luen ; Huang, Huey Chung ; Su, Yi Chun ; Chao, Yee ; Yang, Wen K. ; Whang-Peng, Jacqueline. / Protein tyrosine phosphatase activities are involved in apoptotic cancer cell death induced by GL331, a new homolog of etoposide. In: Cancer Letters. 1996 ; Vol. 110, No. 1-2. pp. 77-85.
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