Polar/apolar chemical inducers of differentiation of transformed cells: strategies to improve therapeutic potential.
- 1 August 1989
- journal article
- research article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences
- Vol. 86 (16), 6358-6362
- https://doi.org/10.1073/pnas.86.16.6358
Abstract
N,N''-Hexamethylenebisacetamide (HMBA) induces transformed cells to differentiate, accompanied by suppression of oncogenicity. Clinical trials have shown that HMBA can cause positive therapeutic responses in some cancer patients, but clinical efficacy may be limited, in part, by dose-related toxicity. Potential improvements in efficacy may be accomplished by changes in the chemical structure of inducing agents and by increasing the sensitivity of tumor cells to inducers of differentiation. We have previously described an approach to improving tumor cell responsiveness to inducing agents. Transformed cell lines that have acquired low levels of resistance to vincristine display a markedly increased sensitivity to HMBA. We now report on a series of hybrid polar/apolar compounds-some of which are as active as HMBA and several of which are significantly more active than HMBA in vitro-whose chemical structures make it likely that they have different pharmacokinetics. Vincristine-resistant murine erythroleukemia cells also are shown to have marked increased sensitivity to these hybrid polar/apolar compounds. Thus these findings suggest potentially useful strategies for the application of polar/apolar inducers of differentiation to the treatment of cancers. These studies also provide approaches to further understanding of the biological process of terminal differentiation.Keywords
This publication has 31 references indexed in Scilit:
- Vincristine-resistant erythroleukemia cell line has marked increased sensitivity to hexamethylenebisacetamide-induced differentiation.Proceedings of the National Academy of Sciences, 1988
- Protein kinase C activity and hexamethylenebisacetamide-induced erythroleukemia cell differentiation.Proceedings of the National Academy of Sciences, 1987
- The Granulocyte-Macrophage Colony-Stimulating FactorsScience, 1985
- Proteases stimulate mouse erythroleukemia cell differentiation and multiplicationBiochemical and Biophysical Research Communications, 1982
- Differentiation of mouse myeloid leukemia cells induced by 1 alpha,25-dihydroxyvitamin D3.Proceedings of the National Academy of Sciences, 1981
- Regulation of normal differentiation in mouse and human myeloid leukemic cells by phorbol esters and the mechanism of tumor promotionProceedings of the National Academy of Sciences, 1979
- Induction of terminal differentiation in human promyelocytic leukemia cells by tumor-promoting agents.Proceedings of the National Academy of Sciences, 1979
- Control of normal cell differentiation and the phenotypic reversion of malignancy in myeloid leukaemiaNature, 1978
- Induction of murine erythroleukemia differentiation by actinomycin DProceedings of the National Academy of Sciences, 1978
- Induction of erythroid differentiation in murine virus infected eythroleukemia cells by highly polar compounds.Proceedings of the National Academy of Sciences, 1975