The natural sweetener metabolite steviol inhibits the proliferation of human osteosarcoma U2OS cell line

Chen,Jun‑Ming; Zhang,Jue; Xia,Yong‑Mei; Wang,Xiao‑Xia; Li,Jian

doi:10.3892/ol.2018.7962

The natural sweetener metabolite steviol inhibits the proliferation of human osteosarcoma U2OS cell line

Authors:
- Jun‑Ming Chen
- Jue Zhang
- Yong‑Mei Xia
- Xiao‑Xia Wang
- Jian Li
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Affiliations: State Key Laboratory of Food Science and Technology, School of Chemical and Materials Engineering, Jiangnan University, Wuxi, Jiangsu 214122, P.R. China, Key Laboratory of Nuclear Medicine of Ministry of Health, Jiangsu Institute of Nuclear Medicine, Wuxi, Jiangsu 214063, P.R. China
Published online on: February 6, 2018 https://doi.org/10.3892/ol.2018.7962
Pages: 5250-5256

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Abstract

Steviol is the colonic metabolite of the natural sweetener steviol glycosides. It does not diffuse to the blood and the half maximal inhibitory concentration of steviol is longer compared with that of current chemotherapy agents, including 5‑fluorouracil and doxorubicin. The present study demonstrated that steviol inhibits the proliferation of the human osteosarcoma U2OS cell line in a dose‑ and time‑dependent manner, and that the inhibition rate is comparative with that of doxorubicin and 5‑fluorouracil. The mechanism of this anticancer activity is also investigated. The results indicated that steviol inhibits U2OS cells through inducing G1 phase cell cycle arrest, downregulating the ability of colony formation via a mitochondrial apoptotic pathway, which was indicated by an increase of the Bax/Bcl‑2 ratio and activation of cyclin‑dependent kinase inhibitor 1, tumor protein 53 and cyclin‑dependent kinase; whereas a Survivin and Caspase 3‑independent mechanism was involved. Considering that steviol appears minimally in the plasma during metabolism, and possesses a median lethal dose of 100-fold greater compared with that of 5‑fluorouracil, it may become a potential chemotherapy agent.

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