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

Wu YH, Chiu WT, Young MJ, Chang TH, Huang YF, Chou CY - J Cancer (2015)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: 1. Department of Obstetrics and Gynecology, College of Medicine, National Cheng Kung University and Hospital, Tainan, 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.

No MeSH data available.


Related in: MedlinePlus

SR-T100 increases mouse xenograft sensitivity to cisplatin. (A) Tumor volumes in A2780CP70 cells. (B) Representative tumor volumes in A2780CP70 cells. (C) Body weight of animals following SR-T100 treatment. PTX: paclitaxel.
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Figure 4: SR-T100 increases mouse xenograft sensitivity to cisplatin. (A) Tumor volumes in A2780CP70 cells. (B) Representative tumor volumes in A2780CP70 cells. (C) Body weight of animals following SR-T100 treatment. PTX: paclitaxel.

Mentions: To determine whether SR-T100 could suppress tumor growth, mice were injected subcutaneously with 1 × 106 A2780CP70 cells and treated with intraperitoneal injection of SR-T100, with or without adding cisplatin (Figs. 4A and 4B) or paclitaxel (Figs. 4D and 4E). When compared to the vehicle controls, single treatment with cisplatin (P = 0.002), varying SR-T100 doses (SR-T100 2.5 mg/kg, P = 0.003; SR-T100 5.0 mg/kg, P = 0.002), or paclitaxel (paclitaxel 2.5 mg/kg, P = 0.001; paclitaxel 5.0 mg/kg, P = 0.001; paclitaxel 10 mg/kg, P = 0.001) significantly inhibited the growth of A2780CP70 cells in mouse xenografts. Moreover, combinations of cisplatin and SR-T100 (SR-T100 2.5 mg/kg + cisplatin 3 mg/kg vs. controls, P = 0.002; SR-T100 5 mg/kg + cisplatin 3 mg/kg vs. controls, P = 0.002) significantly reduced tumor volumes, as compared to the controls. The tumor suppression effect was greater with combination treatment (SR-T100 5 mg/kg and cisplatin 3 mg/kg) than with SR-T100 alone (5 mg/kg alone; P = 0.046). An effect was also found between the combination group and cisplatin alone group (P = 0.032). However, SR-T100 did not significantly increase the sensitivity to paclitaxel in chemoresistant cells (Fig. 4D). The body weight of animals receiving cisplatin, paclitaxel, SR-T100, or combined treatment remained relatively unaltered, suggesting negligible toxicity was observed (Figs. 4C and 4F). These results further confirmed that SR-T100 has the potential to kill chemoresistant cancer cells.


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

Wu YH, Chiu WT, Young MJ, Chang TH, Huang YF, Chou CY - J Cancer (2015)

SR-T100 increases mouse xenograft sensitivity to cisplatin. (A) Tumor volumes in A2780CP70 cells. (B) Representative tumor volumes in A2780CP70 cells. (C) Body weight of animals following SR-T100 treatment. PTX: paclitaxel.
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Related In: Results  -  Collection

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Figure 4: SR-T100 increases mouse xenograft sensitivity to cisplatin. (A) Tumor volumes in A2780CP70 cells. (B) Representative tumor volumes in A2780CP70 cells. (C) Body weight of animals following SR-T100 treatment. PTX: paclitaxel.
Mentions: To determine whether SR-T100 could suppress tumor growth, mice were injected subcutaneously with 1 × 106 A2780CP70 cells and treated with intraperitoneal injection of SR-T100, with or without adding cisplatin (Figs. 4A and 4B) or paclitaxel (Figs. 4D and 4E). When compared to the vehicle controls, single treatment with cisplatin (P = 0.002), varying SR-T100 doses (SR-T100 2.5 mg/kg, P = 0.003; SR-T100 5.0 mg/kg, P = 0.002), or paclitaxel (paclitaxel 2.5 mg/kg, P = 0.001; paclitaxel 5.0 mg/kg, P = 0.001; paclitaxel 10 mg/kg, P = 0.001) significantly inhibited the growth of A2780CP70 cells in mouse xenografts. Moreover, combinations of cisplatin and SR-T100 (SR-T100 2.5 mg/kg + cisplatin 3 mg/kg vs. controls, P = 0.002; SR-T100 5 mg/kg + cisplatin 3 mg/kg vs. controls, P = 0.002) significantly reduced tumor volumes, as compared to the controls. The tumor suppression effect was greater with combination treatment (SR-T100 5 mg/kg and cisplatin 3 mg/kg) than with SR-T100 alone (5 mg/kg alone; P = 0.046). An effect was also found between the combination group and cisplatin alone group (P = 0.032). However, SR-T100 did not significantly increase the sensitivity to paclitaxel in chemoresistant cells (Fig. 4D). The body weight of animals receiving cisplatin, paclitaxel, SR-T100, or combined treatment remained relatively unaltered, suggesting negligible toxicity was observed (Figs. 4C and 4F). These results further confirmed that SR-T100 has the potential to kill chemoresistant cancer cells.

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: 1. Department of Obstetrics and Gynecology, College of Medicine, National Cheng Kung University and Hospital, Tainan, 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.

No MeSH data available.


Related in: MedlinePlus