Next Article in Journal
Editorial to the Special Issue—“Technology for Natural Products Research”
Previous Article in Journal
In Depth Analysis of Kinase Cross Screening Data to Identify CAMKK2 Inhibitory Scaffolds
Open AccessArticle

Tomatidine Represses Invasion and Migration of Human Osteosarcoma U2OS and HOS Cells by Suppression of Presenilin 1 and c-Raf–MEK–ERK Pathway

by Min-Hong Hsieh 1,2,†, Jia-Sin Yang 1,3,†, Renn-Chia Lin 4,5,6, Yi-Hsien Hsieh 7, Shun-Fa Yang 1,3, Horng-Rong Chang 1,5,8,* and Ko-Hsiu Lu 4,5,*
1
Institute of Medicine, Chung Shan Medical University, Taichung 402, Taiwan
2
Department of Orthopedics, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chiayi 622, Taiwan
3
Department of Medical Research, Chung Shan Medical University Hospital, Taichung 402, Taiwan
4
Department of Orthopedics, Chung Shan Medical University Hospital, Taichung 402, Taiwan
5
School of Medicine, Chung Shan Medical University, Taichung 402, Taiwan
6
Division of Hyperbaric Oxygen Therapy and Wound Medicine, Chung Shan Medical University Hospital, Taichung 402, Taiwan
7
Institute of Biochemistry, Microbiology and Immunology, Chung Shan Medical University, Taichung 402, Taiwan
8
Division of Nephrology, Department of Medicine, Chung Shan Medical University Hospital, Taichung 402, Taiwan
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Molecules 2020, 25(2), 326; https://doi.org/10.3390/molecules25020326
Received: 25 November 2019 / Revised: 10 January 2020 / Accepted: 11 January 2020 / Published: 13 January 2020
(This article belongs to the Section Medicinal Chemistry)
Osteosarcoma, which is the most prevalent malignant bone tumor, is responsible for the great majority of bone cancer-associated deaths because of its highly metastatic potential. Although tomatidine is suggested to serve as a chemosensitizer in multidrug-resistant tumors, the anti-metastatic effect of tomatidine in osteosarcoma is still unknown. Here, we tested the hypothesis that tomatidine suppresses migration and invasion, features that are associated with metastatic process in human osteosarcoma cells and also investigate its underlying pathway. Tomatidine, up to 100 μM, without cytotoxicity, inhibited the invasion and migration capabilities of human osteosarcoma U2OS and HOS cells and repressed presenilin 1 (PS-1) expression of U2OS cells. After the knockdown of PS-1, U2OS and HOS cells’ biological behaviors of cellular invasion and migratory potential were significantly reduced. While tomatidine significantly decreased the phosphorylation of c-Raf, mitogen/extracellular signal-regulated kinase (MEK), and extracellular signal-regulated protein kinase (ERK)1/2 in U2OS cells, no obvious influences on p-Jun N-terminal kinase, p38, and Akt, including their phosphorylation, were observed. In ERK 1 silencing U2 OS cells, tomatidine further enhanced the decrease of their migratory potential and invasive activities. We conclude that both PS-1 derived from U2OS and HOS cells and the c-Raf–MEK–ERK pathway contribute to cellular invasion and migration and tomatidine could inhibit the phenomenons. These findings indicate that tomatidine might be a potential candidate for anti-metastasis treatment of human osteosarcoma. View Full-Text
Keywords: ERK; metastasis; osteosarcoma; PS-1; tomatidine ERK; metastasis; osteosarcoma; PS-1; tomatidine
Show Figures

Figure 1

MDPI and ACS Style

Hsieh, M.-H.; Yang, J.-S.; Lin, R.-C.; Hsieh, Y.-H.; Yang, S.-F.; Chang, H.-R.; Lu, K.-H. Tomatidine Represses Invasion and Migration of Human Osteosarcoma U2OS and HOS Cells by Suppression of Presenilin 1 and c-Raf–MEK–ERK Pathway. Molecules 2020, 25, 326.

Show more citation formats Show less citations formats
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
Back to TopTop