Epirubicin induces apoptosis in osteoblasts through death-receptor and mitochondrial pathways

Apoptosis : an International Journal on Programmed Cell Death
Tzu-Ching HuangKee-Lung Chang

Abstract

Epirubicin is an anthracycline and is widely used in tumor treatment, but has toxic and undesirable side effects on wide range of cells and hematopoietic stem cells (HSC). Osteoblasts play important roles in bone development and in supporting HSC differentiation and maturation. It remains unknown whether epirubicin-induced bone loss and hematological toxicity are associated with its effect on osteoblasts. In primary osteoblast cell cultures, epirubicin inhibited cell growth and decreased mineralization. Moreover, epirubicin arrested osteoblasts in the G2/M phase, and this arrest was followed by apoptosis in which both the extrinsic (death receptor-mediated) and intrinsic (mitochondrial-mediated) apoptotic pathways were evoked. The factors involved in the extrinsic apoptotic pathway were increased FasL and FADD as well as activated caspase-8. Those involved in the intrinsic apoptotic pathway were decreased Bcl-2; increased reactive oxygen species, Bax, cytochrome c; and activated caspase-9 and caspase-3. These results demonstrate that epirubicin induced osteoblast apoptosis through the extrinsic and intrinsic apoptotic pathways, leading to the destruction of osteoblasts and consequent lessening of their functions in maintaining ...Continue Reading

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Citations

Jun 17, 2020·Frontiers in Pharmacology·Qing-Xia GanQin-Wan Huang
May 3, 2020·Anti-cancer Agents in Medicinal Chemistry·Yang LuoMinjie Meng
May 1, 2021·Frontiers in Molecular Biosciences·Shulong CaoHaiyuan Zhang

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Methods Mentioned

BETA
protein assay
PCR
electrophoresis
Assay
flow cytometry

Software Mentioned

SAS
Comet Score
Mac Scope
Beacon Designer
WinMDI

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