Next Article in Journal
Immunomonitoring of Tacrolimus in Healthy Volunteers: The First Step from PK- to PD-Based Therapeutic Drug Monitoring?
Previous Article in Journal
Comparison between Fractionated Dose and Single Dose of Cu-64 Trastuzumab Therapy in the NCI-N87 Gastric Cancer Mouse Model
Open AccessArticle

Activating Hippo Pathway via Rassf1 by Ursolic Acid Suppresses the Tumorigenesis of Gastric Cancer

1
Department of Internal Medicine, Chonbuk National University Medical School, Jeonju 54907, Korea
2
Department of Physiology, Chonbuk National University Medical School, Jeonju 54907, Korea
3
Department of Anatomy and Institute for Medical Sciences, Chonbuk National University Medical School, Jeonju 54907, Korea
4
Department of Biochemistry, Chonbuk National University Medical School, Jeonju 54907, Korea
5
Research Institute of Clinical Medicine of Chonbuk National University, Jeonju 54907, Korea
6
Biomedical Research Institute of Chonbuk National University Hospital, Jeonju 54907, Korea
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Int. J. Mol. Sci. 2019, 20(19), 4709; https://doi.org/10.3390/ijms20194709
Received: 27 August 2019 / Revised: 16 September 2019 / Accepted: 18 September 2019 / Published: 23 September 2019
(This article belongs to the Section Biochemistry)
The Hippo pathway is often dysregulated in many carcinomas, which results in various stages of tumor progression. Ursolic acid (UA), a natural compound that exists in many herbal plants, is known to obstruct cancer progression and exerts anti-carcinogenic effect on a number of human cancers. In this study, we aimed to examine the biological mechanisms of action of UA through the Hippo pathway in gastric cancer cells. MTT assay showed a decreased viability of gastric cancer cells after treatment with UA. Following treatment with UA, colony numbers and the sizes of gastric cancer cells were significantly diminished and apoptosis was observed in SNU484 and SNU638 cells. The invasion and migration rates of gastric cancer cells were suppressed by UA in a dose-dependent manner. To further determine the gene expression patterns that are related to the effects of UA, a microarray analysis was performed. Gene ontology analysis revealed that several genes, such as the Hippo pathway upstream target gene, ras association domain family (RASSF1), and its downstream target genes (MST1, MST2, and LATS1) were significantly upregulated by UA, while the expression of YAP1 gene, together with oncogenes (FOXM1, KRAS, and BATF), were significantly decreased. Similar to the gene expression profiling results, the protein levels of RASSF1, MST1, MST2, LATS1, and p-YAP were increased, whereas those of CTGF were decreased by UA in gastric cancer cells. The p-YAP expression induced in gastric cancer cells by UA was reversed with RASSF1 silencing. In addition, the protein levels in the Hippo pathway were increased in the UA-treated xenograft tumor tissues as compared with that in the control tumor tissues; thus, UA significantly inhibited the tumorigenesis of gastric cancer in vivo in xenograft animals. Collectively, UA diminishes the proliferation and metastasis of gastric cancer via the regulation of Hippo pathway through Rassf1, which suggests that UA can be used as a potential chemopreventive and therapeutic agent for gastric cancer. View Full-Text
Keywords: ursolic acid; Hippo signaling; gastric cancer cells; proliferation; metastasis ursolic acid; Hippo signaling; gastric cancer cells; proliferation; metastasis
Show Figures

Figure 1

MDPI and ACS Style

Kim, S.-H.; Jin, H.; Meng, R.Y.; Kim, D.-Y.; Liu, Y.C.; Chai, O.H.; Park, B.H.; Kim, S.M. Activating Hippo Pathway via Rassf1 by Ursolic Acid Suppresses the Tumorigenesis of Gastric Cancer. Int. J. Mol. Sci. 2019, 20, 4709. https://doi.org/10.3390/ijms20194709

AMA Style

Kim S-H, Jin H, Meng RY, Kim D-Y, Liu YC, Chai OH, Park BH, Kim SM. Activating Hippo Pathway via Rassf1 by Ursolic Acid Suppresses the Tumorigenesis of Gastric Cancer. International Journal of Molecular Sciences. 2019; 20(19):4709. https://doi.org/10.3390/ijms20194709

Chicago/Turabian Style

Kim, Seong-Hun; Jin, Hua; Meng, Ruo Y.; Kim, Da-Yeah; Liu, Yu C.; Chai, Ok H.; Park, Byung H.; Kim, Soo M. 2019. "Activating Hippo Pathway via Rassf1 by Ursolic Acid Suppresses the Tumorigenesis of Gastric Cancer" Int. J. Mol. Sci. 20, no. 19: 4709. https://doi.org/10.3390/ijms20194709

Find Other Styles
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Search more from Scilit
 
Search
Back to TopTop