title: Bufalin Inhibits Proliferation and Induces Apoptosis in Osteosarcoma Cells by Downregulating MicroRNA-221.
abstract: Bufalin, a major component of the Chinese medicine ChanSu, which is prepared from the skin and parotid venom glands of toads, has shown cytotoxicity in several malignant tumors. Here, we reported that bufalin inhibited proliferation and induced mitochondria-dependent apoptosis in U-2OS and Saos-2 osteosarcoma cells with intracellular reactive oxygen species (ROS) production. By microRNA (miR) array analysis and quantitative reverse transcription polymerase chain reaction, we found that miR-221 was downregulated after treatment with bufalin. In accordance with TargetScan prediction and luciferase reporter assay, Bcl2 binding component 3 (BBC3) was the direct target of miR-221. Furthermore, upregulating miR-221 by its MIMIC and suppressing BBC3 by small interfering RNA (siRNA) reversed the effects of bufalin on osteosarcoma cells. Collectively, our data indicate that bufalin inhibits cell proliferation and induces mitochondria-dependent apoptosis in osteosarcoma cells through downregulating miR-221 and triggering BBC3 expression.
authors.affiliation: Oncology Department of Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China.
authors.forename: Jianjun
authors.identifier: 0000-0003-3392-7833
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Jin Yang Community Health Service Center, Shanghai 200136, China.
authors.forename: Jingjing
authors.identifier: 0000-0001-7823-6652
authors.initials: J
authors.lastname: Sha
authors.affiliation: Oncology Department of Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China.
authors.forename: Yan
authors.identifier: 0000-0002-5547-2668
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Oncology Department of Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China.
authors.forename: Kun
authors.initials: K
authors.lastname: Han
authors.affiliation: Oncology Department of Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China.
authors.forename: Yaling
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Oncology Department of Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China.
authors.forename: Yang
authors.identifier: 0000-0002-0204-0984
authors.initials: Y
authors.lastname: Su
authors.affiliation: Oncology Department of Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China.
authors.forename: Xiuyi
authors.identifier: 0000-0002-8413-8570
authors.initials: X
authors.lastname: Yin
authors.affiliation: Oncology Department of Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China.
authors.forename: Haiyan
authors.identifier: 0000-0002-3993-974X
authors.initials: H
authors.lastname: Hu
authors.affiliation: Oncology Department of Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China.
authors.forename: Yang
authors.identifier: 0000-0001-7732-4343
authors.initials: Y
authors.lastname: Yao