[Evodiamine induces extrinsic and intrinsic apoptosis of ovarian cancer cells via the mitogen-activated protein kinase/phosphatidylinositol-3-kinase/protein kinase B signaling pathways].

Abstract

OBJECTIVE:

To explore the effects of evodiamine on ovarian cancer cells and the mechanisms underlying such effects.

METHODS:

Human. ovarian cancer cells HO-8910PM were treated with evodiamine at 0, 1.25, 2.5, and 5 μM for 1-4 d. 3-(4,5-Dimethiylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was used to detect the growth inhibition rate of evodiamine-treated HO-8910PM cells. The cell cycle was observed via propidium iodide (PI) staining. Apoptosis induction was assessed via Annexin V-fluorescein isothiocyanate/propidium iodide (Annexin V-FITC/PI) double staining assay. To verify the mechanism of apoptosis, caspase-dependent apoptotic pathway-related protein was detected by Western blot analysis. The expression levels of mitogen-activated protein kinase (MAPK) and/or phosphatidylinositol-3-kinase (PI3K)/protein kinase B (Akt) pathway-related proteins were also investigated.

RESULTS:

Evodiamine significantly inhibited the proliferation of HO-8910PM cells in a dose- and time-dependent manner. Evodiamine induced G2/M arrest with an increase of cyclin B1 level, and promoted cell apoptosis with a decrease of B cell lymphoma/lewkmia-2 (Bcl-2) and an increase of Bcl-2-associated X protein (Bax) level. In addition, evodiamine treatment led to the activation of caspase-8, caspase-9, and caspase-3 and the cleavage of poly (ADP-ribose)-polymerase (PARP). Evodiamine targeted the MAPK and/or PI3K/Akt pathways by reducing the expression and activity of PI3K, Akt, and extracellular signal-regulated kinase mitogen-activated protein kinase (ERK1/2 MAPK) and the activity of p38 MAPK.

CONCLUSION:

Evodiamine can inhibit the growth of ovarian cancer cells by G2/M arrest and intrinsic and extrinsic apoptosis. In addition, evodiamine-induced PI3K/Akt, ERK1/2 MAPK, and p38 MAPK signaling may be involved in cell death.

• Authors: Lijuan Wei, Xiaoying Jin, Zipei Cao, Wenlu Li
• Journal: Journal of traditional Chinese medicine = Chung i tsa chih ying wen pan (J Tradit Chin Med) Vol. 36 Issue 3 Pg. 353-9 (Jun 2016) ISSN: 0255-2922 [Print] China
• PMID: 27468551 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Drugs, Chinese Herbal
• Quinazolines
• evodiamine
• Phosphatidylinositol 3-Kinases
• Proto-Oncogene Proteins c-akt
• Mitogen-Activated Protein Kinases

Topics

• Apoptosis (drug effects)
• Cell Cycle (drug effects)
• Cell Line, Tumor
• Drugs, Chinese Herbal
• Evodia (chemistry)
• Female
• Humans
• MAP Kinase Signaling System (drug effects)
• Mitogen-Activated Protein Kinases (genetics, metabolism)
• Ovarian Neoplasms (drug therapy, enzymology, genetics)
• Phosphatidylinositol 3-Kinases (genetics, metabolism)
• Proto-Oncogene Proteins c-akt (genetics, metabolism)
• Quinazolines (pharmacology)