J Cancer 2015; 6(10):1011-1019. doi:10.7150/jca.12738

Research Paper

Solanum Incanum Extract Downregulates Aldehyde Dehydrogenase 1-Mediated Stemness and Inhibits Tumor Formation in Ovarian Cancer Cells

Yi-Hui Wu1, Wen-Tai Chiu2, Ming-Jer Young3, Tzu-Hao Chang4, Yu-Fang Huang1, Cheng-Yang Chou1✉

1. Department of Obstetrics and Gynecology, College of Medicine, National Cheng Kung University and Hospital, Tainan, Taiwan
2. Department of Biomedical Engineering, National Cheng Kung University, Tainan, Taiwan
3. Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan
4. Graduate Institute of Biomedical Informatics, Taipei Medical University, Taipei, Taiwan

Abstract

Solanum incanum extract (SR-T100), containing the active ingredient solamargine, can induce apoptosis via upregulation of tumor necrosis factor receptor expression and activation of the mitochondrial apoptosis pathway, and has therapeutic effects in patients with actinic keratosis. Here, we evaluate the novel molecular mechanisms underlying SR-T100-regulated stemness and chemoresistance. The concentration of SR-T100 that inhibited 50% cell viability (IC50) was lower in ovarian cancer cells than in nonmalignant cells. Furthermore, the SR-T100 IC50 in chemoresistant cells was similar to the IC50 in chemosensitive cells. Additionally, SR-T100 increased cisplatin and paclitaxel sensitivity in chemoresistant cells. SR-T100 downregulated the expression of stem cell markers, including aldehyde dehydrogenase 1 (ALDH1), Notch1, and FoxM1, and reduced sphere formation in ovarian cancer cells. Using microarray analyses, immunoblotting, luciferase activity, and chromatin immunoprecipitation (ChIP) assays, we showed that SR-T100 suppressed the expression of c/EBPβ and COL11A1, and its promoter activity, in resistant cells, but not sensitive cells. SR-T100, paclitaxel, and cisplatin inhibited the growth of A2780CP70 cells in mouse xenografts, as compared to the vehicle control, and the combination of cisplatin and SR-T100 was more effective than either treatment alone. SR-T100 may represent a potential therapeutic adjunct to chemotherapy for ovarian cancer treatment.

Keywords: Solanum incanum, aldehyde dehydrogenase 1, ovarian cancer, stemness, chemoresistance

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How to cite this article:
Wu YH, Chiu WT, Young MJ, Chang TH, Huang YF, Chou CY. Solanum Incanum Extract Downregulates Aldehyde Dehydrogenase 1-Mediated Stemness and Inhibits Tumor Formation in Ovarian Cancer Cells. J Cancer 2015; 6(10):1011-1019. doi:10.7150/jca.12738. Available from http://www.jcancer.org/v06p1011.htm