Butein induces apoptotic cell death of human cervical cancer cells

Yang,Pei‑Yu; Hu,Dan‑Ning; Kao,Ying‑Hsien; Lin,I‑Ching; Liu,Fu‑Shing

doi:10.3892/ol.2018.9426

Butein induces apoptotic cell death of human cervical cancer cells

Authors:
- Pei‑Yu Yang
- Dan‑Ning Hu
- Ying‑Hsien Kao
- I‑Ching Lin
- Fu‑Shing Liu
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Affiliations: Department of Laboratory, Show Chwan Memorial Hospital, Changhua 50049, Taiwan R.O.C., Tissue Culture Center, New York Eye and Ear Infirmary of Mount Sinai, New York, NY 10003, USA, Department of Medical Research, E‑Da Hospital, Kaohsiung 82445, Taiwan R.O.C., Department of Family Medicine, Changhua Christian Hospital, Changhua 50006, Taiwan R.O.C., Department of Obstetrics and Gynecology, Show Chwan Memorial Hospital, Changhua 50049, Taiwan R.O.C.
Published online on: September 7, 2018 https://doi.org/10.3892/ol.2018.9426
Pages: 6615-6623
Copyright: © Yang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Butein is a chalcone, a flavonoid that is widely biosynthesized in plants. Butein has been identified to possess varied pharmacological activity and is extractable from traditional Chinese medicinal herbs, therefore applicable for disease treatment. Recently, in vitro and in vivo studies have shown that butein may induce apoptotic cell death in various human cancer cells. In this study we investigated the apoptotic effect of butein and the underlying mechanisms in human cervical cancer cells. Two cell lines, C‑33A and SiHa cells, were treated with butein at different dosages for different durations. The effect of butein on cell viability was assessed by MTT assay, which revealed that butein exerted cytotoxicity in both cervical cancer cells in a dose‑ and time‑dependent fashion. Apoptotic pathway‑related factors in the butein‑treated cervical cancer cells were then examined. JC‑1 flow cytometry, cytochrome c assay, and caspase activity assays demonstrated that butein disturbed mitochondrial transmembrane potential, and increased cytosolic cytochrome c levels and caspase activities in both cervical cancer cells. Western blot analysis revealed that butein downregulated anti‑apoptotic protein Bcl‑xL and led to proteolytic cleavage of poly (ADP‑ribose) polymerase. In addition, butein decreased expressions of the inhibitor of apoptosis (IAP) proteins, including X‑linked IAP, survivin, and cellular IAP‑1. The findings of this study suggest that butein can decrease cervical cancer cell viability via a pro‑apoptotic effect, which involves inhibition of the IAP proteins and activation of both extrinsic and intrinsic pro‑apoptotic pathways. Therefore, butein may be applicable for cervical cancer treatment.

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