Enhancement by bufalin of retinoic acid-induced differentiation of acute promyelocytic leukemia cells in primary culture.
Bufalin, a cardiotonic steroid isolated from the Chinese toad venom preparation Chan'su, has differentiation-inducing activity in several myeloid leukemia cell lines. We examined the effect of bufalin on differentiation of leukemic cells from acute myeloid leukemia (AML) patients in primary culture. Bufalin significantly stimulated functional and morphologic differentiation of leukemia cells in four of 20 cases, suggesting that bufalin alone is only a modest inducer of differentiation of AML cells in primary culture. In contrast, acute promyelocytic leukemia (APL) cells showed synergistic differentiation after treatment with all-trans retinoic acid (RA) and bufalin. In some cases, bufalin restored RA sensitivity to previously resistant APL cells. The effective concentration of bufalin for differentiation-inducing activity in APL cells was lower than for its cardiac action. Combined treatment with bufalin and RA may be more effective than RA alone in differentiation therapy of APL.
Department of Hematology, Showa University School of Medicine, Shinagawa, Tokyo, Japan.
K
K
Yamada
K
K
Hino
S
S
Tomoyasu
Y
Y
Honma
N
N
Tsuruoka
D000208:Acute Disease; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002018:Bufanolides / Q000494:pharmacology*; D002316:Cardiotonic Agents / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects; D019008:Drug Resistance, Neoplasm; D004357:Drug Synergism; D005260:Female; D006801:Humans; D007951:Leukemia, Myeloid / Q000473:pathology; D015473:Leukemia, Promyelocytic, Acute / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D014212:Tretinoin / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D002018:Bufanolides; D002316:Cardiotonic Agents; D014212:Tretinoin; C022777:bufalin