Solanum incanum extract downregulates aldehyde dehydrogenase 1-mediated stemness and inhibits tumor formation in ovarian cancer cells

Yi Hui Wu, Wen Tai Chiu, Ming Jer Young, Tzu Hao Chang, Yu Fang Huang, Cheng Yang Chou

Research output: Contribution to journalArticle

8 Citations (Scopus)

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/EBPß 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.

Original languageEnglish
Pages (from-to)1011-1019
Number of pages9
JournalJournal of Cancer
Volume6
Issue number10
DOIs
Publication statusPublished - 2015

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Keywords

  • Aldehyde dehydrogenase 1
  • Chemoresistance
  • Ovarian cancer
  • Solanum incanum
  • Stemness

ASJC Scopus subject areas

  • Oncology

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