Golgi reassembly and stacking protein 65 downregulation is required for the anti-cancer effect of dihydromyricetin on human ovarian cancer cells


Autoři: Fengjie Wang aff001;  Xianbing Chen aff002;  Depei Yuan aff002;  Yongfen Yi aff001;  Yi Luo aff001
Působiště autorů: Department of Pathology, College of Basic Medicine, Chongqing Medical University, Chongqing, China aff001;  Minda Hospital of Hubei Minzu University, Enshi, Hubei, China aff002;  Department of Gynecology and Obstetrics, The First Affiliated Hospital Of Chongqing Medical University, Chongqing, China aff003
Vyšlo v časopise: PLoS ONE 14(11)
Kategorie: Research Article
doi: 10.1371/journal.pone.0225450

Souhrn

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.

Klíčová slova:

Apoptosis – Cancer cell migration – Cancer treatment – Flow cytometry – Ovarian cancer – Small interfering RNAs – Transfection – Golgi apparatus


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2019 Číslo 11