Logo Medical Science Monitor Basic Research

Call: 1.631.470.9640
Mon-Fri 10 am - 2 pm EST

Contact Us

Logo Medical Science Monitor Basic Research Logo Medical Science Monitor Basic Research Logo Medical Science Monitor Basic Research

03 December 2016 : Laboratory Research  

Lysine-Specific Demethylase 1 (LSD1) Inhibitor S2101 Induces Autophagy via the AKT/mTOR Pathway in SKOV3 Ovarian Cancer Cells

Shujun Feng1ABCDE, Ye Jin1BF, Mengjiao Cui1FG, Jianhua Zheng1ADEG*

DOI: 10.12659/MSM.898825

Med Sci Monit 2016; 22:4742-4748

Abstract

BACKGROUND: S2101 is one of the most potent LSD1 inhibitors, which can inhibit ovarian cancer cells viability. This study aimed to detect the mechanism behind the anticancer properties of S2101 in SKOV3 ovarian cells.

MATERIAL AND METHODS: Cell viability was tested by Cell Counting Kit-8 (CCK-8) assay. Cellular apoptosis and autophagy were evaluated by flow cytometric analysis using Annexin-V/PI staining methods and Green fluorescent protein (GFP)-fused-LC3 (GFP-LC3), respectively. Western blotting was performed for analyzing the Bax, Bcl-2, mTOR, p- mTOR, p62, LC3-I, LC3-II, AKT, and p-AKT protein expression.

RESULTS: Our results show that the proportion of early apoptotic and late apoptotic cells increased significantly for cells treated with S2101 at a concentration of 100 μM for 48 h. Treatment of S2101 in SKOV3 cells resulted in upregulation of Bax and downregulation of Bcl-2 in a time-dependent manner, indicating that S2101 can induce apoptosis in SKOV3. There was a downward trend in the expression of p62 when the SKOV3cells were treated with 100 µm S2101 for 12 h, 24 h and 48 h. The conversion of LC3-I to LC3-II was increased significantly at 24 h and 48 h. Autophagy was induced by S2101 in SKOV3 cells, evidenced by an increase in punctuate localization of GFP-LC3 and a change in expression of autophagy-related proteins.

CONCLUSIONS: S2101 treatment decreased the levels of phosphorylated AKT and mTOR. S2101 inhibits SKOV3 cells viability and induces apoptosis and autophagy. The AKT/mTOR signaling pathway was found to be affected by S2101.

Keywords: Autophagy - drug effects, Cell Growth Processes - drug effects, Cell Survival - drug effects, Cyclopropanes - pharmacology, Enzyme Inhibitors - pharmacology, Histone Demethylases - metabolism, Ovarian Neoplasms - pathology, Phenyl Ethers - pharmacology, Proto-Oncogene Proteins c-akt - metabolism, Signal Transduction - drug effects, TOR Serine-Threonine Kinases - metabolism

0 Comments

Most Viewed Current Articles

13 Apr 2020 : Original article  

Outcome of 24 Weeks of Combined Schroth and Pilates Exercises on Cobb Angle, Angle of Trunk Rotation, Chest...

DOI :10.12659/MSMBR.920449

Med Sci Monit Basic Res 2020; 26:e920449

11 May 2020 : Original article  

Analysis of Psychological and Sleep Status and Exercise Rehabilitation of Front-Line Clinical Staff in the ...

DOI :10.12659/MSMBR.924085

Med Sci Monit Basic Res 2020; 26:e924085

05 Jan 2021 : Review article  

A Southeast Asian Perspective on the COVID-19 Pandemic: Hemoglobin E (HbE)-Trait Confers Resistance Against...

DOI :10.12659/MSMBR.929207

Med Sci Monit Basic Res 2021; 27:e929207

10 Aug 2020 : Clinical Research  

Effects of Cognitive Task Training on Dynamic Balance and Gait of Patients with Stroke: A Preliminary Rando...

DOI :10.12659/MSMBR.925264

Med Sci Monit Basic Res 2020; 26:e925264

Your Privacy

We use cookies to ensure the functionality of our website, to personalize content and advertising, to provide social media features, and to analyze our traffic. If you allow us to do so, we also inform our social media, advertising and analysis partners about your use of our website, You can decise for yourself which categories you you want to deny or allow. Please note that based on your settings not all functionalities of the site are available. View our privacy policy.

Medical Science Monitor Basic Research eISSN: 2325-4416
Medical Science Monitor Basic Research eISSN: 2325-4416