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 language | English |
|---|---|
| Pages (from-to) | 1011-1019 |
| Number of pages | 9 |
| Journal | Journal of Cancer |
| Volume | 6 |
| Issue number | 10 |
| DOIs | |
| Publication status | Published - 2015 |
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Keywords
- Aldehyde dehydrogenase 1
- Chemoresistance
- Ovarian cancer
- Solanum incanum
- Stemness
ASJC Scopus subject areas
- Oncology
Cite this
Solanum incanum extract downregulates aldehyde dehydrogenase 1-mediated stemness and inhibits tumor formation in ovarian cancer cells. / Wu, Yi Hui; Chiu, Wen Tai; Young, Ming Jer; Chang, Tzu Hao; Huang, Yu Fang; Chou, Cheng Yang.
In: Journal of Cancer, Vol. 6, No. 10, 2015, p. 1011-1019.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Solanum incanum extract downregulates aldehyde dehydrogenase 1-mediated stemness and inhibits tumor formation in ovarian cancer cells
AU - Wu, Yi Hui
AU - Chiu, Wen Tai
AU - Young, Ming Jer
AU - Chang, Tzu Hao
AU - Huang, Yu Fang
AU - Chou, Cheng Yang
PY - 2015
Y1 - 2015
N2 - 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.
AB - 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.
KW - Aldehyde dehydrogenase 1
KW - Chemoresistance
KW - Ovarian cancer
KW - Solanum incanum
KW - Stemness
UR - http://www.scopus.com/inward/record.url?scp=84947716780&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84947716780&partnerID=8YFLogxK
U2 - 10.7150/jca.12738
DO - 10.7150/jca.12738
M3 - Article
VL - 6
SP - 1011
EP - 1019
JO - Journal of Cancer
JF - Journal of Cancer
SN - 1837-9664
IS - 10
ER -