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

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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 μM). 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.

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Acknowledgements

We would like to thank George Leiman for his assistance with the text and figures. This research was funded by the Intramural Research Program of the NIH, Center for Cancer Research, National Cancer Institute.

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Author notes

  1. Xing-Jie Liang

    Present address: Division of Nanomedicine and Nanobiology, National Center of Nanoscience and Technology, Zhongguancun, 100080, Beijing, China

Authors and Affiliations

  1. Laboratory of Cell Biology, National Cancer Institute, NIH, Bethesda, MD, 20892, USA

    Xing-Jie Liang, Ding-Wu Shen, Michael M. Gottesman & Adorjan Aszalos

  2. Instrumentation and Biophysics Branch, Center for Food Safety and Applied Nutrition, Food and Drug Administration, College Park, MD, 20740, USA

    Jun-Jie Yin

  3. Laboratory of Cancer Biology and Genetics, NIH, Bethesda, MD, 20892, USA

    Barbara Taylor

  4. Laboratory of Experimental Carcinogenesis, NIH, Bethesda, MD, 20892, USA

    Stephen M. Winkovitch & Susan H. Garfield

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  1. Xing-Jie Liang
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Correspondence to Adorjan Aszalos.

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Liang, XJ., Yin, JJ., Taylor, B. et al. Disruption of microfilaments by cytochalasin B decreases accumulation of cisplatin in human epidermal carcinoma and liver carcinoma cell lines. Cancer Chemother Pharmacol 62, 977–984 (2008). https://doi.org/10.1007/s00280-008-0687-9

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  • DOI: https://doi.org/10.1007/s00280-008-0687-9

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