Abstract
Ovarian cancer remains the most lethal gynecological malignant tumor. In this study, 24 xanthones were isolated and identified from the pericarps of mangosteen (Garcinia mangostana), and their anti-proliferative activities were tested in ovarian cancer cells. Garcinone E (GE) was found to exhibit excellent anti-proliferative effects among the tested xanthones. It significantly inhibited the proliferation in HEY, A2780, and A2780/Taxol cells as evidenced by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay, lactate dehydrogenase (LDH) release assay, Hoechst 33342 staining, annexin V/PI staining, and JC-1 staining. It induced endoplasmic reticulum (ER) stress and activated the protective inositol-requiring kinase (IRE)-1α pathway. Knocking down IRE-1α further activated the caspase cascade and caused an increase in cell death. Moreover, GE eliminated the migratory ability of HEY cells by reducing the expression of RhoA and Rac. It also blocked the invasion, which might be related to downregulation of matrix metalloproteinases (MMPs), i.e., MMP-9 and MMP-2, and upregulation of tissue inhibitors of metalloproteinase (TIMP) -1 and TIMP-2. In summary, GE exerts anticancer activities by inducing apoptosis and suppressing migration and invasion in ovarian cancer cells, which indicates its therapeutic potential for ovarian cancer.
Highlights
With a five-year survival rate that remained below 40% for decades, ovarian cancer is considered to be the most lethal gynecological malignant tumor in the world1
The resistance index on garcinone E (GE) was 1.12 (Fig. 2B). These results suggest that did GE exhibit promising anti-proliferative effects, but it demonstrated a similar activity in the multidrug-resistant cell line compared to its parental sensitive cell line, which indicated a potential anti-multidrug-resistant prospect in ovarian cancer cells
In vitro and in vivo studies of α-mangostin show that it has many types of anticancer mechanisms including apoptosis-induction16, endoplasmic reticulum (ER) stress-stimulation22, autophagy-regulation25, and matrix metalloproteinases (MMPs)-suppression26
Summary
With a five-year survival rate that remained below 40% for decades, ovarian cancer is considered to be the most lethal gynecological malignant tumor in the world. Α-Mangostin is known as one of the primary xanthones, which has been thoroughly studied; we found that garcinone E (GE) exerted similar and possibly enhanced anticancer properties in the tested cancer cell lines. We isolated 24 xanthones from mangosteen pericarps and tested their anti-proliferative effects via 3-(4,5-dimethylthiazol-2-yl)2,5-diphenyl tetrazolium bromide (MTT) assay. It demonstrated some anti-proliferative effects in several cancer cell lines, its anticancer mechanism has not yet been well determined. This study would be focused on the anti-ovarian cancer effects and mechanisms of GE
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
