Antitumor Activity of Magainin Analogues against Human Lung Cancer Cell Lines

Yoshinobu Ohsaki, Adi F. Gazdar, Hao Chia Chen, Bruce E. Johnson

Research output: Contribution to journalArticle

142 Scopus citations

Abstract

Magainin 1 and magainin 2, originally isolated from African clawed frog Xenopus laevis skin, inhibit the growth of bacteria and fungi. Synthetic magainin A (MAG A) and magainin G (MAG G) are more potent against bacteria and protozoa. In order to determine the antitumor activity of these analogues, we have tested these two analogues against six small cell lung cancer (SCLQ cell lines NCI-H82, NCI-H526, NCI-H678, NCI-H735, NCI-H841, and NCI-H889, which were known to differ by more than 10-fold in their sensitivity to different chemothera-peutic agents, and four normal human fibroblast cell lines. Semiauto-mated 3-(4,5-dimethylthiazoI-2-yl)-2,5-diphenyltetrazolium bromide as-says of the six SCLC cell lines revealed average concentrations producing 50% inhibition (IQo) values of 2.6 MM (range, 0.49-930 MM) for cisplatin, 2.5 MM (range, 039-6.00 MM) for etoposide, and 138.8 nM (range, 55.0450.0 nM) for doxorubicin. The average IQo of MAG A was 8.64 MM (range, 6.23-11.7 MM) and that of MAG G was 8.82 MM (range, 4.4412.5 MM) against the SCLC cell lines. Despite a 10-fold difference in sensitivity to standard chemotherapeutic agents, the IQo of MAG A and MAG G differs by <3-fold. The average IQo against four normal human fibroblast cell lines was 21.1 MM (range, 12.7-25.6 MM) for MAG A and 29.2 MM (range, 213-34.8 MM) for MAG G. Combined exposure to the IQo concentration of MAG A or MAG G plus IQo of etoposide or cisplatin decreased the percentage of surviving SCLC cells to 29.0% (range, 26.1-31.7%). MAG A or MAG G had an additive effect when used with standard chemotherapeutic agents. These data suggest that MAG A and MAG G have in vitro antitumor activity against SCLC cell lines.

Original languageEnglish (US)
Pages (from-to)3534-3538
Number of pages5
JournalCancer research
Volume52
Issue number13
StatePublished - Jul 1992

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Ohsaki, Y., Gazdar, A. F., Chen, H. C., & Johnson, B. E. (1992). Antitumor Activity of Magainin Analogues against Human Lung Cancer Cell Lines. Cancer research, 52(13), 3534-3538.