Tamoxifen enhances the differentiation-inducing and growth-inhibitory effects of all-trans retinoic acid in acute promyelocytic leukemia cells

International Journal of Oncology
Koji AdachiJunji Suzumiya

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.

References

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Citations

Aug 7, 2018·World Journal of Hepatology·Riccardo InchingoloDavide Ippolito
Apr 12, 2020·Cancers·Alessia Roma, Paul A Spagnuolo
Aug 28, 2021·International Journal of Molecular Sciences·Miguel Olivas-AguirreOxana Dobrovinskaya

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