Juglone exerts antitumor effect in ovarian cancer cells

Document Type : Original Article


1 Department of Immunology, Jilin Medical College, Jilin, Jilin, China

2 Department of Narcotization, Affiliated Hospital of Jilin Medical College, Jilin, Jilin, China

3 Department of Pathology, Jilin Medical College, Jilin, Jilin, China

4 Department of Urology Surgery, Affiliated Hospital of Jilin Medical College, Jilin, Jilin, China


Objective(s): Juglone is isolated from many species of the Juglandaceae family and used as an anti-viral, anti-bacterial, and anti-tumor therapeutic. Here, we evaluated juglone-induced antitumor effect in ovarian cancer SKOV3 cells.
Materials and Methods: MTT assay was performed to examine juglone anti-proliferative effect. Cell cycle and apoptosis were studied using flow cytometry in juglone-treated SKOV3 cells. To investigate molecular mechanism of cell cycle and apoptosis, protein expression levels were measured by Western blot analysis of cyclin D1, Bcl-2, Bax, cytochrome c, caspase-9 and caspase-3. To investigate the motility of juglone-treated SKOV3 cell, Matrigel invasion assay was employed to characterize cell invasion. Also, matrix metalloproteinase-2 (MMP-2) expression levels were detected by western blot.
Results:Juglone significantly inhibited SKOV3 cell proliferation as shown by G0/G1 phase arrest, and this effect was mediated by inactivation of cyclin D1 protein (P<0.05). Juglone induced apoptosis in SKOV3 cell which was accompanied by caspase-9 and caspase-3 activation (P<0.05). Juglone decreased Bcl-2 levels and increased Bax and cytochrome c (Cyt c) levels(P<0.05). Juglone sufficiently inhibited invasion while evidently decreased MMP-2 expression (P<0.05).
Conclusion:The results suggest that juglone could probably induce apoptosis through mitochondrial pathway and restrained cell invasiveness by decreasing MMP expression.


1. Della Pepa C, Banerjee S. Bevacizumab in combination with chemotherapy in platinum-sensitive ovarian cancer. Onco Targets Ther 2004; 7:1025-1032.
2. Sytykiewicz H. Expression patterns of glutathione transferase gene (GstI) in maize seedlings under juglone-induced oxidative stress. Int J Mol Sci 2011; 12:7982-7985.
3. Bertin C, Yang X, Weson LA. The role of root exudates and allelochemicals in the rhizosphere. Plant Soil 2003; 256:67-83.
4. Cenas N, Prast S, Nivinskas H, Sarlauskas J, Arner ES. Interactions of nitroaromatic compounds with the mammalian selenoprotein thioredoxin reductase and the relation to induction of apoptosis in human cancer cells. J Biol Chem 2006; 281:5593-5603.
5. Xu HL, Yu XF, Qu SC, Qu XR, Jiang YF, Sui da Y. Juglone, from Juglans mandshruica Maxim, inhibits growth and induces apoptosis in human leukemia cell HL-60 through a reactive oxygen species-dependent mechanism. Food Chem Toxicol 2012; 50: 590-596.
6. Zhang W, Liu A, Li Y, Zhao X, Lv S, Zhu W, et al. Anticancer activity and mechanism of juglone on human cervical carcinoma Hela cells. Can J Pharmacol 2012; 90:1553-1558.
7. Richard J Y, Andreas S. The BCL-2 protein family: opposing activities that mediate cell death. Nat Rev Mol Cell Biol 2008; 9:47-59.
8. Lamb J, Ramaswamy S, Ford HL, Contreras B, Martinez RV, Kittrell FS, et al. A mechanism of cyclin D1 action encoded in the patterns of gene expression in human cancer. Cell 2003; 114,323–334.
9. Takahashi A, Kimura F, Yamanaka A, Takebayashi A, Kita N, Takahashi K, et al. Metformin impairs growth of endometrial cancer cells via cell cycle arrest and concomitant autophagy and apoptosis. Cancer Cell Int 2014; 14:53.
10. Seervi M, Joseph J, Sobhan PK, Bobhan PK, Bhavya BC, Santhoshkumar TR. Essential requirement of cytochrome c release for caspase activation by procaspase-activating compound defined by cellular models. Cell Death Dis 2011; 8:e207.
11. Lengvel E. Ovarian cancer development and metastasis. Am J Pathol 2010; 177:1053-1064.
12. Itoh Y, Nagase H. Matrix metalloproteinases in cancer. Essays Biochem 2002; 38:21-36.