Disruption of microfilaments by cytochalasin B decreases accumulation of cisplatin in human epidermal carcinoma and liver carcinoma cell lines.

Abstract

BACKGROUND:

Although cisplatin is a frequently used cancer chemotherapeutic drug, its effectiveness is hindered by the development of resistance in cancer cells. In order to understand the reason(s) for this resistance, the mechanism of uptake of cisplatin into cells must be characterized. While several previous studies showed structural differences between cisplatin-sensitive and resistant cells, the influence of microfilaments, known to affect transport of molecules into cells, and the influence of certain biophysical characteristics of the plasma membrane needed clarification.

RESULTS:

We show that resistant human epidermal carcinoma (KB-CP20) and liver carcinoma (BEL-7404-CP20) cells become relatively more resistant if their already weak microfilaments are degraded by cytochalasin B treatment (.5-2 microM). The sensitive counterparts of these cells with intact microfilaments are not significantly affected by this treatment. We also show that the "fluidity" of the plasma membrane and the membrane potential of the sensitive and resistant cells studied do not appear to influence the uptake of cisplatin into the cells.

CONCLUSION:

Our results suggest that the status of the microfilament system influences the mechanism of uptake of cisplatin into cells.

• Authors: Xing-Jie Liang, Jun-Jie Yin, Barbara Taylor, Stephen M Winkovitch, Susan H Garfield, Ding-Wu Shen, Michael M Gottesman, Adorjan Aszalos
• Journal: Cancer chemotherapy and pharmacology (Cancer Chemother Pharmacol) Vol. 62 Issue 6 Pg. 977-84 (Nov 2008) ISSN: 1432-0843 [Electronic] Germany
• PMID: 18274748 (Publication Type: Journal Article, Research Support, N.I.H., Intramural)

Chemical References

• Cytochalasin B
• Cisplatin

Topics

• Actin Cytoskeleton (drug effects, physiology)
• Biological Transport (drug effects)
• Carcinoma (metabolism, pathology)
• Carcinoma, Hepatocellular (metabolism, pathology)
• Cell Division (drug effects)
• Cell Line, Tumor (drug effects, metabolism)
• Cell Membrane Permeability (drug effects)
• Cisplatin (metabolism, pharmacology)
• Cytochalasin B (pharmacology)
• Drug Resistance, Neoplasm (drug effects)
• Humans
• KB Cells (drug effects, metabolism)
• Liver Neoplasms (metabolism, pathology)
• Membrane Fluidity (drug effects)
• Membrane Potentials (drug effects)
• Skin Neoplasms (metabolism, pathology)