Chen Jun-Ming, Zhang Jue, Xia Yong-Mei, Wang Xiao-Xia, Li Jian
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.
Oncol Lett. 2018 Apr;15(4):5250-5256. doi: 10.3892/ol.2018.7962. Epub 2018 Feb 6.
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.
甜菊醇是天然甜味剂甜菊糖苷的结肠代谢产物。它不会扩散到血液中，与包括5-氟尿嘧啶和阿霉素在内的现有化疗药物相比，甜菊醇的半数最大抑制浓度持续时间更长。本研究表明，甜菊醇以剂量和时间依赖性方式抑制人骨肉瘤U2OS细胞系的增殖，其抑制率与阿霉素和5-氟尿嘧啶相当。还对这种抗癌活性的机制进行了研究。结果表明，甜菊醇通过诱导G1期细胞周期停滞来抑制U2OS细胞，通过线粒体凋亡途径下调集落形成能力，这表现为Bax/Bcl-2比值增加以及细胞周期蛋白依赖性激酶抑制剂1、肿瘤蛋白53和细胞周期蛋白依赖性激酶激活；然而，这涉及一种不依赖生存素和半胱天冬酶3的机制。鉴于甜菊醇在代谢过程中在血浆中出现的量极少，并且其半数致死剂量比5-氟尿嘧啶大100倍，它可能成为一种潜在的化疗药物。
