A natural food sweetener with anti-pancreatic cancer properties.

C Liu,D-Q Dou,L-Q Ma,L-H Dai,Y-X Sun

doi:10.1038/oncsis.2016.28

Abstract

Mogroside V is a triterpenoid isolated from the traditional Chinese medical plant Siraitia grosvenorii. Mogroside V has a high degree of sweetness and a low calorific content. Herein, we found that mogroside V possesses tumor growth inhibitory activity in in vitro and in vivo models of pancreatic cancer by promoting apoptosis and cell cycle arrest of pancreatic cancer cells (PANC-1 cells), which may in part be mediated through regulating the STAT3 signaling pathway. These results were confirmed in vivo in a mouse xenograft model of pancreatic cancer. In xenograft tumors, Ki-67 and PCNA, the most commonly used markers of tumor cell proliferation, were downregulated after intravenous administration of mogroside V. Terminal deoxynucleotidyl transferase dUTP nick end labeling assays showed that mogroside V treatment promoted apoptosis of pancreatic cancer cells in the xenograft tumors. Furthermore, we found that mogroside V treatment significantly reduced the expression of CD31-labeled blood vessels and of the pro-angiogenic factor vascular endothelial growth factor in the xenografts, indicating that mogroside V might limit the growth of pancreatic tumors by inhibiting angiogenesis and reducing vascular density. These results therefore demonstrate that the natural, sweet-tasting compound mogroside V can inhibit proliferation and survival of pancreatic cancer cells via targeting multiple biological targets.

Highlights

Cancer poses an important threat to human health, and seriously affects the quality of life
To further determine whether the antiproliferative effects of mogroside V were related to the induction of apoptosis and/or necrosis, mogroside V-treated cells were analyzed with terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assays
We further found that z-VAD-fmk, a general caspase inhibitor, inhibited apoptosis of PANC-1 cells induced by treatment with mogroside V for 48 h (Figure 2c)

Summary

INTRODUCTION

Cancer poses an important threat to human health, and seriously affects the quality of life. Drugs included in the Pharmacopoeia of the People's Republic of China,[3] which lists the main effects of S. grosvenorii as 'heat-releasing and lung-moistening, beneficial to the pharynx and voice, facilitating to bowel movement and acting as a laxative.' Currently, studies on S. grosvenorii are focused on its antioxidant,[4,5] anti-inflammatory[6] and blood lipid- and sugarreducing potential.[7] far, the numerous studies on S. grosvenorii have not been sufficiently comprehensive They have failed to provide a clear mechanism of action and to characterize the full pharmacological effects of this medicinal plant. S. grosvenorii inhibited pancreatic cancer cell proliferation and survival through the STAT3 pathway both in vivo and in vitro These results indicate that mogroside V may be a promising increase in the G0/G1 ratio was observed, reaching a 1.7-fold anticancer drug for daily use with relatively few side effects. Increase after exposure to the highest dose (250 μmol/l) compared with that in the untreated cells (Figure 2d)

RESULTS

DISCUSSION

MATERIALS AND METHODS

CONFLICT OF INTEREST

Commission C