A novel podophyllotoxin-derived compound GL331 is more potent than its congener VP-16 in killing refractory cancer cells

Tze Sing Huang, Chun Chung Lee, Yee Chao, Chih Hung Shu, Li Tzong Chen, Li Li Chen, Min Hsiung Chen, Chiou Chung Yuan, Jacqueline Whang-Peng

Research output: Contribution to journalArticle

56 Citations (Scopus)

Abstract

Purpose. GL331 is a new homolog of VP- 16, and has demonstrated more efficacious anti-cancer activity in both the in vitro and in vivo lymphoma systems. To extensively explore GL331 's clinical value, we furthermore evaluate the cytotoxicity and apoptosis-inducing activity of GL331 in several human cell lines from cancers that are not normally treated with VP-16. Methods. By MTT and clonogenic survival assays, the cytotoxicities of GL331 and VP-16 were evaluated in a variety of cell lines including nasopharyngeal, hepatocellular, gastric, colon, cervical, and neuroblastoma cancer types. Western blot analysis was performed to detect the MDR-1 level in these cell lines. By Annexin V-staining flow cytometry and detection of DNA ladders, the apoptosis-inducing activities of GL331 and VP-16 were also evaluated. Results. GL331 showed more efficacy than its congener VP-16 in killing cancer cells. The estimated ID50 of GL331 were 2.5 to 17-fold lower than those of VP-16. GL331 possessed more cell-killing activity even in MDR-1- overexpressing cell lines such as HCC36 and SW620. Its higher cytotoxicity could be attributed by the elevated ability to induce apoptotic cell death. Conclusion. GL331's overriding drug resistance and higher cancer cell-killing activity suggest its superiority in clinical cancer therapy.

Original languageEnglish
Pages (from-to)997-1002
Number of pages6
JournalPharmaceutical Research
Volume16
Issue number7
DOIs
Publication statusPublished - Jan 1 1999
Externally publishedYes

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Keywords

  • Apoptosis
  • Cytotoxicity
  • GL33 I
  • VP- 16

ASJC Scopus subject areas

  • Biotechnology
  • Molecular Medicine
  • Pharmacology
  • Pharmaceutical Science
  • Organic Chemistry
  • Pharmacology (medical)

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