title: Tamoxifen enhances the differentiation-inducing and growth-inhibitory effects of all-trans retinoic acid in acute promyelocytic leukemia cells.
abstract: All-trans retinoic acid (ATRA) is valuable in differentiation therapy for acute promyelocytic leukemia (APL). However, ATRA has had limited success as a single agent, due to the development of resistance. We found that tamoxifen effectively enhanced the differentiation-inducing effect of ATRA. Tamoxifen alone inhibited the proliferation of myeloid leukemia cell lines while only slightly increasing morphologic differentiation. Tamoxifen effectively enhanced the growth-inhibiting actions of various differentiation-inducing agents. ATRA in the presence of tamoxifen increased NBT reduction and the expression of CD11b in HL-60 cells more effectively than ATRA alone. Tamoxifen also enhanced the differentiation induced by the other inducers tested. ATRA induced the differentiation of APL cell lines NB4 and HT93 and APL cells in primary culture, and this differentiation was also enhanced by tamoxifen. Tamoxifen is one of the most widely used drugs for the treatment of cancer and has few side effects. The combination of ATRA and tamoxifen might be considered for the treatment of APL patients in whom it can be difficult to apply arsenic trioxide or anthracyclines.
authors.affiliation: Department of Oncology/Hematology, School of Medicine, Shimane University, Izumo, Shimane 693-8501, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Adachi
authors.affiliation: Department of Oncology/Hematology, School of Medicine, Shimane University, Izumo, Shimane 693-8501, Japan.
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Honma
authors.affiliation: Department of Oncology/Hematology, School of Medicine, Shimane University, Izumo, Shimane 693-8501, Japan.
authors.forename: Takaaki
authors.initials: T
authors.lastname: Miyake
authors.affiliation: Department of Oncology/Hematology, School of Medicine, Shimane University, Izumo, Shimane 693-8501, Japan.
authors.forename: Koshi
authors.initials: K
authors.lastname: Kawakami
authors.affiliation: Department of Oncology/Hematology, School of Medicine, Shimane University, Izumo, Shimane 693-8501, Japan.
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Takahashi
authors.affiliation: Department of Oncology/Hematology, School of Medicine, Shimane University, Izumo, Shimane 693-8501, Japan.
authors.forename: Junji
authors.initials: J
authors.lastname: Suzumiya
mesh_terms: D000818:Animals; D018943:Anthracyclines / Q000737:chemistry; D018931:Antineoplastic Agents, Hormonal / Q000737:chemistry; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000737:chemistry; D001854:Bone Marrow Cells / Q000166:cytology; D039481:CD11b Antigen / Q000378:metabolism; D002454:Cell Differentiation; D002455:Cell Division; D045744:Cell Line, Tumor / Q000187:drug effects; D049109:Cell Proliferation; D002470:Cell Survival; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D015973:Gene Expression Regulation, Leukemic; D018922:HL-60 Cells / Q000187:drug effects; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000473:pathology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008875:Middle Aged; D010087:Oxides / Q000737:chemistry; D013629:Tamoxifen / Q000737:chemistry*; D014212:Tretinoin / Q000737:chemistry*
chemical_list: D018943:Anthracyclines; D018931:Antineoplastic Agents, Hormonal; D001152:Arsenicals; D039481:CD11b Antigen; C509295:ITGAM protein, human; D010087:Oxides; D013629:Tamoxifen; D014212:Tretinoin; D048049:Extracellular Signal-Regulated MAP Kinases; D000077237:Arsenic Trioxide