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- Monk Fruit (Siraitia grosvenorii [Swingle], Cucurbitaceae)
- Mogroside V
- Pancreatic Cancer
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Date:
07-15-2016 | HC# 061631-548
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Re: Mogroside V, a Compound of Monk Fruit, Inhibits Pancreatic Cancer Cell Proliferation and Promotes Tumor Apoptosis In Vivo and In Vitro
Liu C, Dai LH, Dou DQ, Ma LQ, Sun YX. A natural food
sweetener with anti-pancreatic cancer properties. Oncogenesis. April 2016;5:e217. doi:
10.1038/oncsis.2016.28.
Much oncology research involves searching for more effective
and less toxic chemotherapy drugs. Screening of plants for bioactive compounds can
supply drug development leads, but is costly and time-consuming. These authors
suggest that plants with long histories of medicinal use, such as those used in
Chinese medicine, should be prioritized for study. Among those plants is monk
fruit [luo han guo; Siraitia grosvenorii
(Swingle), Cucurbitaceae]. According to the article, the Pharmacopoeia of the People's Republic of China lists the benefits
of monk fruit as "heat-releasing and lung-moistening," relieving
throat and vocal problems, and laxative activity.
Monk fruit saponins were approved in 1997 by the Chinese
Ministry of Health for use as a sweetener in foods. The effect of these compounds
in pancreatic cancer was of interest because patients with that disease should limit
sugar intake, and might substitute other natural sweeteners. In this study,
these authors examined the effects of mogroside V (Sigma-Aldrich; St. Louis,
Missouri), a triterpene glycoside, on the proliferation and viability of PANC-1
(human pancreatic carcinoma, epithelial-like) cells
(Shanghai Cell Biology Institute; Shanghai, China) in vitro and in vivo.
PANC-1 cells were incubated with mogroside V at concentrations
of 0 µmol/L to 250 µmol/L. The MTT assay, terminal deoxynucleotidyl transferase
dUTP nick end labeling (TUNEL) assays, and flow cytometry were used to measure
proliferation and apoptosis. Several other cell lines were subjected to comparable
MTT assays. Western blot assays were used to examine the effects on the signal
transducer and activator of transcription 3 (STAT3) signaling pathway, which
contributes to cell growth and proliferation and may be involved in the development
of several types of cancer.1,2
In vivo activity was assessed in a xenograft model in which eight-week-old
male BALB/c mice (Charles River Ltd. Co.; Beijing, China) were subcutaneously
injected with PANC-1 cells. Five groups of six mice were treated three times
weekly with 2, 10, or 30 mg/kg body weight of intravenous mogroside V, normal
saline, or no treatment. Tumor volumes were estimated every five days from
measurements with calipers; after five weeks, the mice were sacrificed, tumors
were weighed and measured, and vascularization was examined in stained
sections. Real-time polymerase chain reaction was used in fresh tumor tissue to
measure expression of PCNA and Ki-67, markers of tumor cell
proliferation, and paraffin-embedded sections were stained using monoclonal
antibodies for those genes.
Results revealed that mogroside V reduced proliferation and
increased apoptosis in PANC-1 cells and most of the other cell lines tested;
the effect was both concentration- and time-dependent. (The only cell line that
showed very little reduction in cell proliferation, CFPAC-1, was another of the
pancreatic adenocarcinoma lines tested.) Treatment of PANC-1 cells with
mogroside V reduced phosphorylation of STAT3 and two kinases upstream of STAT3 in
the same pathway, increasing expression of two cyclin kinase inhibitors,
associated with cell cycle arrest, and two pro-apoptotic proteins.
In the mouse xenograft model, all doses significantly reduced
tumor growth, with higher doses more effective, and survival to the end of the
study was improved. Mean tumor volume, based on postmortem measurement, was
stated to be 278.6 ± 0.03 mm3 in control mice versus 56.4 ± 0.11 mm3
in the mice receiving 30 mg/kg doses of mogroside V (P<0.001). Tumor weight
in the same groups was 32.2 ± 1.4 g versus 9.2 ± 1.8 g (P<0.001). Expression
of PCNA and Ki-67 in tumor tissues was significantly reduced with mogroside V
treatment (P<0.001 for all doses relative to the control group, with higher
doses most effective). Mogroside V also inhibited angiogenesis and the
expression of vascular endothelial growth factor (VEGF), which plays a role in
angiogenesis,3,4 with the highest dose most effective (P<0.001
vs. control).
Mogroside
V may act against pancreatic cancer by multiple mechanisms, increasing
apoptosis while inhibiting cell proliferation and angiogenesis, perhaps in part
by inhibiting the STAT3 pathway. In future studies, the authors plan to
investigate this further by exploring the efficacy of mogroside V when STAT3 is
stably overexpressed or deleted in the PANC-1 cells used in xenografts. The
authors say that mogroside V has been approved by the United States Food and
Drug Administration as a sweetener, and suggest that its use might reduce the
risk of pancreatic cancer. [Note: A March 2016 Generally Recognized as Safe
(GRAS) notice for S. grosvenorii (Swingle) fruit extract is listed as
"pending" as of this writing.]
―Shari Henson
References
1Bromberg JF,
Wrzeszczynska MH, Devgan G, et al. Stat3 as an oncogene. Cell. 1999;98(3):295-303.
2Darnell JE. Validating
Stat3 in cancer therapy. Nat Med.
2005;11(6):595-596.
3Neufeld G, Cohen T,
Gengrinovitch S, Poltorak Z. Vascular endothelial growth factor (VEGF) and its
receptors. FASEB J. 1999;13(1):9-22.
4Holash J, Maisonpierre
PC, Compton D, et al. Vessel cooption, regression, and growth in tumors
mediated by angiopoietins and VEGF. Science.
1999;284(5422):1994-1998.
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