Second generation hybrid polar compounds are potent inducers of transformed cell differentiation
Richon, VM; Webb, Y; Merger, R; Sheppard, T; Jursic, B; Ngo, L; Civoli, F; Breslow, R; Rifkind, RA; Marks, PA
| HERO ID | 4932978 |
|---|---|
| In Press | No |
| Year | 1996 |
| Title | Second generation hybrid polar compounds are potent inducers of transformed cell differentiation |
| Authors | Richon, VM; Webb, Y; Merger, R; Sheppard, T; Jursic, B; Ngo, L; Civoli, F; Breslow, R; Rifkind, RA; Marks, PA |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Volume | 93 |
| Issue | 12 (June 11 |
| Page Numbers | 5705-5708 |
| Abstract | Hybrid polar compounds, of which hexamethylenebisacetamide (HMBA) is the prototype, are potent inducers of differentiation of murine erythroleukemia (MEL) cells and a wide variety of other transformed cells. HMBA has been shown to induce differentiation of neoplastic cells in patients, but is not an adequate therapeutic agent because of dose-limiting toxicity. We report on a group of three potent second generation hybrid polar compounds, diethyl bis-(pentamethylene-N,N-dimethylcarboxamide) malonate (EMBA), suberoylanilide hydroxamic acid (SAHA), and m-carboxycinnamic acid bis-hydroxamide (CBHA) with optimal concentrations for inducing MEL cells of 0.4 mM, 2 microM, and 4 microM, respectively, compared to 5 mM for HMBA. All three agents induce accumulation of underphosphorylated pRB; increased levels of p2l protein, a prolongation of the initial G1 phase of the cell cycle; and accumulation of hemoglobin. However, based upon their effective concentrations, the cross-resistance or sensitivity of an HMBA-resistant MEL cell variant, and differences in c-myb expression during induction, these differentiation-inducing hybrid polar compounds can be grouped into two subsets, HMBA/EMBA and SAHA/CBHA. This classification may prove of value in selecting and planning prospective preclinical and clinical studies toward the treatment of cancer by differentiation therapy. |
| Doi | 10.1073/pnas.93.12.5705 |
| Pmid | 8650156 |
| Wosid | WOS:A1996UQ45500007 |
| Is Certified Translation | No |
| Dupe Override | No |
| Is Public | Yes |
| Language Text | English |
| Keyword | Index Medicus; 1996) |