Costunolide Inhibits the Growth of OAW42-A Multidrug-Resistant Human Ovarian Cancer Cells by Activating Apoptotic and Autophagic Pathways, Production of Reactive Oxygen Species (ROS), Cleaved Caspase-3 and Cleaved Caspase-9
Authors: Jie Li
Yinan Wu
Yichen Fang
Yang Shen
Jing Gui
Journal: Medical Science Monitor (2019)
Discipline: CLINICAL MEDICINE
Keywords: ovarian cancer; costunolide; cell growth; apoptosis; autophagy
Affiliations: Department of Gynecologic Oncology, Jiangsu Cancer Hospital and Jiangsu Institute of Cancer Research and The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, Jiangsu, China (mainland)., Department of Gynecology, Women's Hospital of Nanjing Medical University, Nanjing Maternity and Child Health Care Hospital, Nanjing, Jiangsu, China (mainland)., Department of Pathology, Jiangsu Cancer Hospital and Jiangsu Institute of Cancer Research and The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, Jiangsu, China (mainland)., Department of Obstetrics, Women's Hospital of Nanjing Medical University, Nanjing Maternity and Child Health Care Hospital, Nanjing, Jiangsu, China (mainland).

Abstract:  BACKGROUND Worldwide, ovarian cancer has a high mortality rate due to the difficulty in diagnosing early-stage disease and resistance to chemotherapy agents. Costunolide is a plant-derived sesquiterpene lactone with anti-oxidant properties. This study aimed to investigate the effects of costunolide on cell growth, apoptosis, autophagy, the production of reactive oxygen species (ROS), cleaved caspase-3, and cleaved caspase-9 on the multidrug-resistant ovarian cancer cell line, OAW42-A. MATERIAL AND METHODS The MTT assay determined the proliferation rate of OAW42-A multidrug-resistant ovarian cancer cells and the apoptosis rate was determined using propidium iodide (PI) staining. Autophagy was detected by measuring the expression of LC3 II. Fluorescence flow cytometry was used to measure the levels of reactive oxygen species (ROS) and the mitochondrial membrane potential. Protein expression of LC3 II, beclin 1, cleaved caspase-3, and cleaved caspase-9 were measured by Western blot. RESULTS Costunolide treatment inhibited the growth of OAW42-A cells with an IC₅₀ of 25 µM, resulted in apoptotic cell death, increased the expression of Bax, and decreased the expression of Bcl-2. Confocal electron microscopy showed that costunolide induced autophagy in the OAW42-A cells. Western blot showed that costunolide treatment of OAW42-A cells increased the expression of the LC3 II, beclin 1, cleaved caspase-3, and cleaved caspase-9. Costunolide treatment significantly increased the levels of ROS and reduced the OAW42-A cell mitochondrial membrane potential. CONCLUSIONS Costunolide inhibited growth, apoptosis, ROS generation, and was associated with loss of mitochondrial membrane potential of OAW42-A multidrug-resistant ovarian cancer cells. 

Retracted: Yes

PubPeer comments:
  A total of 93 HCC and adjacent normal tissues were collected from Henan Provincial Peopleu2019s Hospital. All tissues were evaluated by two independent and experienced pathologists. This is the only source of patient-survival data that I could see. Fig 1D.  The survival curve of HCC patients based on median circ-FOXP1 expression in HCC tissues. ![file] Figs 4G, 5G.  The survival curve of HCC patients with high or low SOX expression ...  The survival curve of HCC patients with high or low miR-875-3p miR-421 expression. ![file] 1D on one hand, and 4G, 5G on the other hand, seem to have come from completely different data sets. Have I missed something? , 
 #2 Many thanks, that resolves my confusion. , 
 #3 Comment #2 seems to have disappeared, taking with it an explanation of the data-source used to derive Figs 4G and 5G. Could the authors repeat it? , 
 #5 http: kmplot.com analysis index.php?p=service ![file] ,