Antitumor activity of magainin analogues against human lung cancer cell lines

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

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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 (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-dimetbylthiazol-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.

Original languageEnglish (US)
Pages (from-to)3534-3538
Number of pages5
JournalCancer Research
Volume52
Issue number13
StatePublished - Jul 1 1992

Fingerprint

Magainins
Lung Neoplasms
Small Cell Lung Carcinoma
Inhibitory Concentration 50
Cell Line
Etoposide
Cisplatin
Fibroblasts
Bacteria
Xenopus laevis
magainin A
Bromides
Anura
Doxorubicin
magainin G
Fungi
Skin

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

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.

Antitumor activity of magainin analogues against human lung cancer cell lines. / Ohsaki, Yoshinobu; Gazdar, Adi F.; Chen, Hao Chia; Johnson, Bruce E.

In: Cancer Research, Vol. 52, No. 13, 01.07.1992, p. 3534-3538.

Research output: Contribution to journalArticle

Ohsaki, Y, Gazdar, AF, Chen, HC & Johnson, BE 1992, 'Antitumor activity of magainin analogues against human lung cancer cell lines', Cancer Research, vol. 52, no. 13, pp. 3534-3538.
Ohsaki Y, Gazdar AF, Chen HC, Johnson BE. Antitumor activity of magainin analogues against human lung cancer cell lines. Cancer Research. 1992 Jul 1;52(13):3534-3538.
Ohsaki, Yoshinobu ; Gazdar, Adi F. ; Chen, Hao Chia ; Johnson, Bruce E. / Antitumor activity of magainin analogues against human lung cancer cell lines. In: Cancer Research. 1992 ; Vol. 52, No. 13. pp. 3534-3538.
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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 (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-dimetbylthiazol-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.",
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N2 - 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-dimetbylthiazol-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.

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