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Mechanism of Transport and Intracellular Binding of Porfiromycin in HCT 116 Human Colon Carcinoma Cells¹

University of Maryland Cancer Center, Baltimore, Maryland 21201

The mechanism of uptake and efflux of porfiromycin (PFM) by HCT 116 human colon carcinoma cells or freshly obtained human RBC was investigated. The time course of uptake of radioactivity upon exposure of HCT 116 cells to [¹⁴C]PFM showed one fast and one slow phase of linear increase. The initial phase of PFM uptake was not saturable with external drug concentrations from 2 to 100 µM. PFM accumulation was temperature dependent with a temperature coefficient (Q₁₀ 24–37°C) of 2.3 ± 0.3. PFM uptake was not affected either by individual inhibitors such as 1 mM 2,4-dinitrophenol, sodium azide, iodoacetic acid, ouabain, 0.02 mM oligomycin, p-hydroxylmercuribenzoate, 0.2 mM N-ethylmaleimide, or by combinations of inhibitors. PFM uptake did not demonstrate competitive inhibition by unlabeled PFM and mitomycin C. Efflux of cellular radioactivity was not affected by the above mentioned inhibitors or by verapamil, diltiazem, or trifluoperazine. Only aliphatic alcohols accelerated the initial influx rate. The RBC, however, only exhibited the initial fast accumulation of [¹⁴C]PFM, and all of the ¹⁴C accumulated by RBC was exchangeable. These data demonstrate that the uptake and the efflux of PFM in HCT 116 cells and RBC comprise a passive diffusion process.

¹ This work was supported partly by Grant CA33697 from the NIH and partly by Grant CH-412 from the American Cancer Society.

² To whom requests for reprints should be addressed.

Received 2/ 8/89. Revised 5/12/89. Accepted 6/20/89.