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Differential sensitivity of leukemic and normal hematopoietic progenitors to the killing effect of hyperthermia and quercetin used in combination: Role of heat‐shock protein‐70
Author(s) -
Larocca Luigi M.,
Ranelletti Franco O.,
Maggiano Nicola,
Rutella Sergio,
La Barbera Elettra Ortu,
Rumi Carlo,
Serra Fabio,
Voso Maria T.,
Piantelli Mauro,
Teofili Luciana,
Leone Giuseppe
Publication year - 1997
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/(sici)1097-0215(19970926)73:1<75::aid-ijc13>3.0.co;2-4
Subject(s) - progenitor cell , haematopoiesis , cd34 , apoptosis , cancer research , heat shock protein , bone marrow , biology , transplantation , ex vivo , quercetin , stem cell , immunology , in vivo , pharmacology , medicine , microbiology and biotechnology , biochemistry , genetics , gene , antioxidant
Autologous bone‐marrow transplantation (ABMT) is widely used in the treatment of acute leukemias where a matched sibling donor is not available for allogeneic transplantation. However, a major problem in ABMT is relapse, and ex vivo purging may be very important in preventing it. We show here that quercetin enhances the growth‐inhibitory effect of hyperthermia (HT) in AML (19 cases) and ALL (6 cases) leukemic blasts. Furthermore, the inhibitory effect of this combined treatment resulted in leukemic‐cell apoptosis. On the contrary, normal hematopoietic progenitors were neither growth‐inhibited nor induced to apoptosis by HT‐plus‐quercetin treatment. To explain this difference in sensitivity of leukemic and normal hematopoietic progenitors, we analyzed the effect of quercetin on heat‐induced expression of heat‐shock protein‐70 (HSP‐70), which has been shown to be important in regulating thermosensitivity. We found that quercetin inhibits heat‐induced HSP‐70 expression both at protein and at mRNA levels in AML and ALL blasts. In normal CD34 + progenitors, the combined treatment with HT and quercetin did not reduce HSP‐70 expression and did not induce cell apoptosis. Considering the difference in heat sensitivity of normal CD34 + and leukemic progenitors in the presence of quercetin, the combined use of HT and quercetin could constitute a purging protocol for ABMT. Int. J. Cancer 73:75–83, 1997. © 1997 Wiley‐Liss, Inc.