Cytotoxicity of combinations of prostaglandin D2(PGD2) and antitumor drugs for B16 melanoma cells in culture
✍ Scribed by Bijoy K. Bhuyan; Gloria J. Badiner; Earl G. Adams; Robin Chase
- Publisher
- Springer US
- Year
- 1986
- Tongue
- English
- Weight
- 578 KB
- Volume
- 4
- Category
- Article
- ISSN
- 0167-6997
No coin nor oath required. For personal study only.
✦ Synopsis
Prostaglandin D 2 (PGD2) is lethal to murine and human melanoma cells at high doses, but synchronizes cells at G 1 at non-toxic doses (2.5 or 5/xg/ml). We tested the lethality to B16 mouse melanoma cells of combinations of PGD 2 with anticancer drugs. The drugs selected were mostly those used in treating human melanoma: actinomycin D, Bleomycin, BCNU, cis-platin, melphalan, 5-fluorouracil, and 1-~-D-arabinofuranosylcytosine (ara-C). PGD 2 was combined with the drugs according to 3 different protocols:
Protocol 1 An asynchronous culture was given a long term (24 hr) exposure simultaneously to PGD 2 + drug. Combinations with Bleomycin, ara-C or melphalan were additive or slightly antagonistic whereas PGD 2 plus actinomycin D was significantly antagonistic.
Protocol 2
Cells synchronized in G 1 by 24 hr PGD 2 exposure were then given a short-term (2 hr) treatment with PGD 2 + drug. Combinations with cis-platin, Bleomycin, BCNU or 5-fluorouracil were additive or slightly antagonistic, whereas melphalan and actinomycin D combinations were significantly antagonistic.
Protocol 3
Cells were released from a PGD2-induced G 1 block and were exposed to drug at different times during cell progression. Actinomycin D was antagonistic when added immediately after release from the G 1 block, but was significantly synergistic when added 10 to 12 hr later.
The effect of the combinations cannot be explained by available cell cycle or biochemical information. The antagonism between PGD 2 and several of the drugs resembles the "cytoprotective" effect of PGD 2 towards various noxious agents.