Inducing differentiation of transformed cells with hybrid polar compounds: A cell cycle-dependent process Journal Article

   


Authors: Marks, P. A.; Richon, V. M.; Kiyokawa, H.; Rifkind, R. A.
Article Title: Inducing differentiation of transformed cells with hybrid polar compounds: A cell cycle-dependent process
Abstract: Transformed cells do not necessarily lose their capacity to differentiate. Various agents can induce many types of neoplastic cells to terminal differentiation. Among such inducers, a particularly potent group consists of hybrid polar compounds; hexamethylene bisacetamide (HMBA) is the prototype of this group. With virus-transformed murine erythroleukemia cells as a model, HMBA was shown to cause these cells to arrest in G1 phase and express globin genes. This review focuses on HMBA-induced modulation of factors regulating G1-to-S phase progression, including a decrease in the G1 cyclin-dependent kinase cdk4, associated with inhibition of phosphorylation of the retinoblastoma protein pRB and possibly other related proteins that, in turn, sequester factors required for initiation of DNA synthesis; this provides a possible mechanism for HMBA-induced terminal cell division. Evidence that hybrid polar compounds have therapeutic potential for cancer treatment will also be reviewed.
Keywords: clinical article; protein phosphorylation; acute granulocytic leukemia; human cell; clinical trial; review; nonhuman; antineoplastic agents; dna synthesis; animal cell; mouse; animal; mice; cell cycle; cell division; phase 2 clinical trial; gene expression; thrombocytopenia; transcription factor; cell differentiation; tumor cells, cultured; structure-activity relationship; cancer therapy; animalia; myelodysplastic syndrome; dna; cell transformation; globin; globin gene; murinae; cell line, transformed; protein kinase c; phase 1 clinical trial; cycline; cyclin-dependent kinases; cyclins; retinoblastoma protein; clinical trials; phorbol 13 acetate 12 myristate; leukemia, erythroblastic, acute; hexamethylenebisacetamide; acetamides; human; priority journal; support, non-u.s. gov't; support, u.s. gov't, p.h.s.; erythroleukemia cell; elongation factor 2
Journal Title: Proceedings of the National Academy of Sciences of the United States of America
Volume: 91
Issue: 22
ISSN: 0027-8424
Publisher: National Academy of Sciences  
Date Published: 1994-10-25
Start Page: 10251
End Page: 10254
Language: English
DOI: 10.1073/pnas.91.22.10251
PUBMED: 7937935
PROVIDER: scopus
PMCID: PMC44997
DOI/URL:

https://www.scopus.com/inward/record.uri?eid=2-s2.0-0028116705&doi=10.1073%2fpnas.91.22.10251&partnerID=40&md5=5888f02784326bf6103b865b3b18475e
Notes: Source: Scopus
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MSK Authors
  1. Victoria M Richon
    91 Richon
  2. Paul Marks
    186 Marks
  3. Richard Rifkind
    118 Rifkind
  4. Hiroaki Kiyokawa
    27 Kiyokawa
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