Steviol, a natural product inhibits proliferation of the gastrointestinal cancer cells intensively

// Junming Chen 1, 2 , Yongmei Xia 1, 2, 3 , Xiaochen Sui 1, 2 , Qingrui Peng 1, 2 , Tongtong Zhang 1, 2 , Jian Li 4 and Jue Zhang 4 1 State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu 214122, China 2 Key Laboratory of Synthetic and Biological Colloids (Ministry of Education), School of Chemical and Materials Engineering, Jiangnan University, Wuxi, Jiangsu 214122, China 3 International Joint Laboratory on Food Safety, Jiangnan University, Wuxi, Jiangsu 214122, China 4 Key Laboratory of Nuclear Medicine of Ministry of Health, Jiangsu Institute of Nuclear Medicine, Wuxi, Jiangsu 214063, China Correspondence to: Yongmei Xia, email: ymxia@jiangnan.edu.cn Keywords: steviol; steviol glycoside; cancer; gastrointestinal Received: September 13, 2017 Accepted: March 24, 2018 Published: May 29, 2018 ABSTRACT New anticancer agents with lower toxicity have been always urged because of drug resistance associated with overused chemotherapy agents. In this study, steviol, a colonic metabolite of natural sweetener and also a component in leaves of stevia rebaudiana bertoni , was found to possess intensive anticancer activity on the human gastrointestinal cancer cells. Steviol inhibited six human gastrointestinal cancer cells intensively as 5-fluorouracil did at 100 μg/mL. The inhibition mechanism follows mitochondrial apoptotic pathway that was evidenced by increase of Bax/Bcl-2 ratio, activation of p21 and p53; and caspase 3-independent mechanism was also involved. These results are consistent with the miRNA expression analysis. The most regulated miRNAs in the steviol treated gastrointestinal cancer cells were miR-203a-3p (log2 =1.32) and miR-6088 (log2 =-2.54) in HCT-116, miR-1268b (log2 =19.85) and miR-23c (log2 =-2.05) in MKN-45. In view of the metabolic characteristics of steviol and its cytotoxicity on the cancer cells, steviol could be a chemotherapy agent potentially for cancer treatment.