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Golgi reassembly and stacking protein 65 downregulation is required for the anti-cancer effect of dihydromyricetin on human ovarian cancer cells
- Source :
- PLoS ONE, PLoS ONE, Vol 14, Iss 11, p e0225450 (2019)
- Publication Year :
- 2019
- Publisher :
- Public Library of Science, 2019.
-
Abstract
- Golgi reassembly and stacking protein 65 (GRASP65), which has been involved in cancer progression, is associated with tumor growth and cell apoptosis. Dihydromyricetin (DHM) has demonstrated antitumor activity in different types of human cancers. However, the pharmacological effects of DHM on ovarian cancer (OC) and the molecular mechanisms that underlie these effects are largely unknown. The present study showed that DHM reduced cell migration and invasion in a concentration- and time-dependent manner and induced cell apoptosis primarily through upregulation of Cleaved-caspase-3 and the Bax/Bcl-2 ratio in OCs. To further clarify the cancer therapeutic target, we assessed the effect of DHM on the expression of GRASP65, which is overexpressed in human ovarian cancer tissues. DHM activated caspase-3 and decreased GRASP65 expression to promote cell apoptosis, implying that downregulation of GRASP65 was related to DHM-induced cell apoptosis. Additionally, the knockdown of GRASP65 by siRNA resulted in increased apoptosis after DHM treatment, while western blot and flow cytometry analysis demonstrated that overexpression of GRASP65 attenuated DHM-mediated apoptosis. In addition, the JNK/ERK pathway may be involved in DHM-mediated caspase-3 activation and GRASP65 downregulation. Taken together, these findings provide novel evidence of the anti-cancer properties of DHM in OCs, indicating that DHM is a potential therapeutic agent for ovarian cancer through the inhibition of GRASP65 expression and the regulation of JNK/ERK pathway.
- Subjects :
- 0301 basic medicine
MAPK/ERK pathway
Flavonols
Cancer Treatment
Golgi Apparatus
Apoptosis
Biochemistry
0302 clinical medicine
Spectrum Analysis Techniques
Cell Movement
Medicine and Health Sciences
Small interfering RNAs
RNA, Small Interfering
Ovarian Neoplasms
Gene knockdown
Multidisciplinary
Secretory Pathway
Cell Death
Chemistry
Caspase 3
Cell migration
Flow Cytometry
Ovarian Cancer
Cancer Cell Migration
Up-Regulation
Nucleic acids
Cell Motility
Oncology
Proto-Oncogene Proteins c-bcl-2
Cell Processes
Spectrophotometry
030220 oncology & carcinogenesis
Medicine
Female
RNA Interference
Cytophotometry
Cellular Structures and Organelles
Research Article
MAP Kinase Signaling System
Science
Down-Regulation
Antineoplastic Agents
Cell Migration
Transfection
Research and Analysis Methods
03 medical and health sciences
Downregulation and upregulation
Cell Line, Tumor
medicine
Genetics
Humans
Non-coding RNA
Molecular Biology Techniques
Molecular Biology
Cancer
Biology and Life Sciences
Cancers and Neoplasms
Golgi Matrix Proteins
Cell Biology
medicine.disease
Gene regulation
030104 developmental biology
Cell culture
Cancer research
RNA
Gene expression
Ovarian cancer
Gynecological Tumors
Developmental Biology
Subjects
Details
- Language :
- English
- ISSN :
- 19326203
- Volume :
- 14
- Issue :
- 11
- Database :
- OpenAIRE
- Journal :
- PLoS ONE
- Accession number :
- edsair.doi.dedup.....c2993ca9d009c2e46818f87424049f1d