New designed HMBA agents as inducers of erythroleukemia cell differentiation.

Abstract

OBJECTIVE:

Searching for more potent and less toxic HMBA-related agents.

METHODS:

Human erythroleukemia cell K562, murine erythroleukemia cell (MEL) and its sub-line MEL DS19 were used as target cells to select a cell line which is the most sensitive to HMBA, then analyzed the activity of inducing differentiation of two new designed HMBA derivatives: HMBPA [hexamethylenebi (3-pyridin) amide] and Co-HDTA (ethylenediaminetetra acetic acid cobalt) using cell biology, cytochemical and molecular biology techniques.

RESULTS:

We found that the MEL DS19 cells were most sensitive to HMBA (benzidine positive, B+ approximately 76%). Co-HDTA can inhibit the growth of MEL DS19, but induces differentiation just in a small population (B+ 2% approximately 4.5%). Between 0.02 approximately 5 micromol/L, HMBPA induces 3% approximately 8% cells committed to differentiation with little inhibition of cell proliferation. 1 micromol/L HMBPA and 2 mmol/L HMBA together, can obviously increase the percentage of differentiated cell (B+ approximately 72%), inhibit DNA synthesis and accelerate beta-globin transcription.

CONCLUSION:

The new HMBA derivatives may provide potential cancer differentiation inducers.

• Authors: Huali Wang, Shifu Zhang, Jianping Zhou, Jingbo Zhang
• Journal: Chinese medical sciences journal = Chung-kuo i hsueh k'o hsueh tsa chih (Chin Med Sci J) Vol. 17 Issue 1 Pg. 27-31 (Mar 2002) ISSN: 1001-9294 [Print] China
• PMID: 12894881 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Acetamides
• Antineoplastic Agents
• Pyridines
• RNA, Messenger
• hexamethylenebi (3-pyridin) amide
• Globins
• hexamethylene bisacetamide

Topics

• Acetamides (chemistry, pharmacology)
• Animals
• Antineoplastic Agents (pharmacology)
• Cell Differentiation (drug effects)
• Cell Division (drug effects)
• Globins (biosynthesis, genetics)
• Humans
• K562 Cells
• Leukemia, Erythroblastic, Acute (metabolism, pathology)
• Mice
• Pyridines (chemistry, pharmacology)
• RNA, Messenger (genetics)
• Tumor Cells, Cultured