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Antitumor Activity of Magainin Analogues against Human Lung Cancer Cell Lines¹

National Cancer Institute-Navy Medical Oncology Branch, National Cancer Institute, National Institutes of Health, National Naval Medical Center, Bethesda, Maryland 20889-5105 [Y. O., A. F. G., B. E. J.], and Endocrinology and Reproduction Research Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892 [H-C. C]

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 (SCLC) 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 chemotherapeutic agents, and four normal human fibroblast cell lines. Semiautomated 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays of the six SCLC cell lines revealed average concentrations producing 50% inhibition (IC₅₀) values of 2.6 µM (range, 0.49–9.30 µM) for cisplatin, 2.5 µM (range, 0.39–6.00 µM) for etoposide, and 138.8 nM (range, 55.0–450.0 nM) for doxorubicin. The average IC₅₀ of MAG A was 8.64 µM (range, 6.23–11.7 µM) and that of MAG G was 8.82 µM (range, 4.44–12.5 µM) against the SCLC cell lines. Despite a 10-fold difference in sensitivity to standard chemotherapeutic agents, the IC₅₀ of MAG A and MAG G differs by <3-fold. The average IC₅₀ against four normal human fibroblast cell lines was 21.1 µM (range, 12.7–25.6 µM) for MAG A and 29.2 µM (range, 21.3–34.8 µM) for MAG G. Combined exposure to the IC₅₀ concentration of MAG A or MAG G plus IC₅₀ 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.

¹ This work was supported in part by a generous grant from the Schissler Foundation. The opinions or assertions contained herein are the private views of the authors and are not to be construed as official or as reflecting the views of the Department of the Navy or the Department of Defense. This is a U.S. government work. There are no restrictions on its use.

² To whom requests for reprints should be addressed, at National Cancer Institute-Navy Medical Oncology Branch, National Naval Medical Center, Bldg. 8, Rm. 5101, Bethesda, MD 20889-5105.

Received 10/24/91. Accepted 4/24/92.

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