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Antiproliferative effects of free and liposome-encapsulated retinoic acid in a squamous carcinoma model: monolayer cells and multicellular tumor spheroids

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  • Experimental Oncology
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Summary

Antiproliferative effects of free retinoic acid (RA) and liposome-encapsulated RA (RAlp) were compared in a squamous carcinoma system using both monolayer cells and multicellular tumor spheroids (MTS), an in-vivo-like model with three-dimensional histological structure. Initial studies examined the effect of lipid composition on the efficiency of RA encapsulation and on the subsequent toxicity of RAlp to red blood cells. In 5-day growth assays for monolayer cells, RA and RAlp (1 μM-0.1 nM) produced similar growth inhibition. In 6-day growth assays for MTS, RAlp was shown to have increased effectiveness. Liposomal uptake by the squamous carcinoma cells was examined by culturing monolayers and MTS with fluorescence-tagged liposomes and examining them under fluorescence microscopy between days 1 and 6. Phagocytosed liposomes were present, but their low levels suggested that other mechanisms of drug delivery such as adsorption, fusion or direct lipid transfer probably occurred for RAlp. Histological examination of MTS showed that RA and RAlp produced similar alterations. In this squamous carcinoma system, liposomes are effective in delivering retinoic acid and in producing biological effects in monolayer cells and within the three-dimensional structure of MTS.

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Abbreviations

MTS:

multicellular tumor spheroids

SCC:

squamous cell carcinoma

RA free:

β-all-trans-retinoic acid

RAlp:

lipo-some-encapsulated RA

PtdCho:

dimyristoylglycerophosphocholine

PtdGro:

dimyristoylglycerophosphoglycerol

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Authors and Affiliations

  1. Department of Tumor Biology, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Blvd., 77030, Houston, TX, USA

    Peter G. Sacks & Victor Oke

  2. Department of Head and Neck Surgery, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Blvd., 77030, Houston, TX, USA

    Peter G. Sacks

  3. Department of Clinical Immunology and Biological Therapy, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Blvd., 77030, Houston, TX, USA

    Kapil Mehta

Authors
  1. Peter G. Sacks
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  2. Victor Oke
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  3. Kapil Mehta
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Additional information

This work was supported in part by M. D. Anderson Annual Campaign Funds and by United States Public Health Service grants CA38751 and CA57166 from the National Cancer Institute

Present address: Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York; NY 10021, USA

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Sacks, P.G., Oke, V. & Mehta, K. Antiproliferative effects of free and liposome-encapsulated retinoic acid in a squamous carcinoma model: monolayer cells and multicellular tumor spheroids. J Cancer Res Clin Oncol 118, 490–496 (1992). https://doi.org/10.1007/BF01225262

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  • DOI: https://doi.org/10.1007/BF01225262

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