Anti-tumor effects of the ethanolic extract of Trichosanthes kirilowii seeds in colorectal cancer
Background Trichosanthis semen, the seeds of Trichosanthes kirilowii Maxim. or Trichosanthes rosthornii Harms, has long been used in Korean medicine to loosen bowels and relieve chronic constipation. Although the fruits and radixes of this medicinal herb and their constituents have been reported to...
Ausführliche Beschreibung
Autor*in: |
Park, Su Mi [verfasserIn] |
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E-Artikel |
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Sprache: |
Englisch |
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2019 |
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Anmerkung: |
© The Author(s) 2019 |
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Übergeordnetes Werk: |
Enthalten in: Chinese medicine - London : BioMed Central, 2006, 14(2019), 1 vom: 07. Okt. |
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Übergeordnetes Werk: |
volume:14 ; year:2019 ; number:1 ; day:07 ; month:10 |
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DOI / URN: |
10.1186/s13020-019-0263-8 |
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Katalog-ID: |
SPR02947678X |
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520 | |a Background Trichosanthis semen, the seeds of Trichosanthes kirilowii Maxim. or Trichosanthes rosthornii Harms, has long been used in Korean medicine to loosen bowels and relieve chronic constipation. Although the fruits and radixes of this medicinal herb and their constituents have been reported to exhibit therapeutic effects in various cancers, the anti-cancer effects of its seeds have been relatively less studied. In this study, we investigated the effects of an ethanolic extract of T. kirilowii seeds (TKSE) against colorectal cancer and its mechanism. Methods The anti-tumor effects of the TKSE were evaluated in HT-29 and CT-26 colorectal cancer cells and in a CT-26 tumor-bearing mouse model. Results TKSE suppressed the growth of HT-29 and CT-26 cells (both colorectal cancer cell lines) and the cytotoxic effect of TKSE was greater than that of 5-fluorouracil (5-Fu) in HT-29 cells. TKSE significantly induced mitochondrial membrane potential loss in HT-29 and CT-26 cells and dose-dependently inhibited Bcl-2 expression and induced the cleavages of caspase-3 and PARP. In particular, TKSE at 300 µg/mL induced nuclear condensation and fragmentation in HT-29 cells. Furthermore, TKSE dose-dependently inhibited activations of the Akt/mTOR and ERK pathways, and markedly induced the phosphorylation of AMPK. An AMPKα inhibitor (compound C) effectively blocked the TKSE-induced mitochondrial dysfunction. In addition, TKSE attenuated the hypoxia-inducible factor-1α/vascular endothelial growth factor signaling pathway in HT-29 cells under hypoxic-mimic conditions and inhibited migration and invasion. Oral administration of TKSE (100 or 300 mg/kg) inhibited tumor growth in a mouse CT-26 allograft model but was not as effective as 5-Fu (the positive control), which was administered intraperitoneally. In the same model, 5-Fu caused significant body weight loss, but no such loss was observed in TKSE-treated mice. Conclusion Taken together, these results suggest TKSE has potent anti-tumor effects which might be partly due to the activation of AMPK, and the induction mitochondrial-mediated apoptosis in colorectal cancer cells. These findings provide scientific evidence supporting the potential use of TKSE as a complementary and alternative medicine for the treatment of colorectal cancer. | ||
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10.1186/s13020-019-0263-8 doi (DE-627)SPR02947678X (SPR)s13020-019-0263-8-e DE-627 ger DE-627 rakwb eng Park, Su Mi verfasserin aut Anti-tumor effects of the ethanolic extract of Trichosanthes kirilowii seeds in colorectal cancer 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2019 Background Trichosanthis semen, the seeds of Trichosanthes kirilowii Maxim. or Trichosanthes rosthornii Harms, has long been used in Korean medicine to loosen bowels and relieve chronic constipation. Although the fruits and radixes of this medicinal herb and their constituents have been reported to exhibit therapeutic effects in various cancers, the anti-cancer effects of its seeds have been relatively less studied. In this study, we investigated the effects of an ethanolic extract of T. kirilowii seeds (TKSE) against colorectal cancer and its mechanism. Methods The anti-tumor effects of the TKSE were evaluated in HT-29 and CT-26 colorectal cancer cells and in a CT-26 tumor-bearing mouse model. Results TKSE suppressed the growth of HT-29 and CT-26 cells (both colorectal cancer cell lines) and the cytotoxic effect of TKSE was greater than that of 5-fluorouracil (5-Fu) in HT-29 cells. TKSE significantly induced mitochondrial membrane potential loss in HT-29 and CT-26 cells and dose-dependently inhibited Bcl-2 expression and induced the cleavages of caspase-3 and PARP. In particular, TKSE at 300 µg/mL induced nuclear condensation and fragmentation in HT-29 cells. Furthermore, TKSE dose-dependently inhibited activations of the Akt/mTOR and ERK pathways, and markedly induced the phosphorylation of AMPK. An AMPKα inhibitor (compound C) effectively blocked the TKSE-induced mitochondrial dysfunction. In addition, TKSE attenuated the hypoxia-inducible factor-1α/vascular endothelial growth factor signaling pathway in HT-29 cells under hypoxic-mimic conditions and inhibited migration and invasion. Oral administration of TKSE (100 or 300 mg/kg) inhibited tumor growth in a mouse CT-26 allograft model but was not as effective as 5-Fu (the positive control), which was administered intraperitoneally. In the same model, 5-Fu caused significant body weight loss, but no such loss was observed in TKSE-treated mice. Conclusion Taken together, these results suggest TKSE has potent anti-tumor effects which might be partly due to the activation of AMPK, and the induction mitochondrial-mediated apoptosis in colorectal cancer cells. These findings provide scientific evidence supporting the potential use of TKSE as a complementary and alternative medicine for the treatment of colorectal cancer. Trichosanthis semen (dpeaa)DE-He213 Colorectal cancer (dpeaa)DE-He213 Anti-cancer (dpeaa)DE-He213 Apoptosis (dpeaa)DE-He213 Anti-tumor (dpeaa)DE-He213 Jeon, Sang Kyu aut Kim, Ok Hyeon aut Ahn, Jung Yun aut Kim, Chang-Hyun aut Park, Sun-Dong aut Lee, Ju-Hee (orcid)0000-0003-4147-9794 aut Enthalten in Chinese medicine London : BioMed Central, 2006 14(2019), 1 vom: 07. Okt. (DE-627)521457025 (DE-600)2260322-0 1749-8546 nnns volume:14 year:2019 number:1 day:07 month:10 https://dx.doi.org/10.1186/s13020-019-0263-8 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 14 2019 1 07 10 |
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10.1186/s13020-019-0263-8 doi (DE-627)SPR02947678X (SPR)s13020-019-0263-8-e DE-627 ger DE-627 rakwb eng Park, Su Mi verfasserin aut Anti-tumor effects of the ethanolic extract of Trichosanthes kirilowii seeds in colorectal cancer 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2019 Background Trichosanthis semen, the seeds of Trichosanthes kirilowii Maxim. or Trichosanthes rosthornii Harms, has long been used in Korean medicine to loosen bowels and relieve chronic constipation. Although the fruits and radixes of this medicinal herb and their constituents have been reported to exhibit therapeutic effects in various cancers, the anti-cancer effects of its seeds have been relatively less studied. In this study, we investigated the effects of an ethanolic extract of T. kirilowii seeds (TKSE) against colorectal cancer and its mechanism. Methods The anti-tumor effects of the TKSE were evaluated in HT-29 and CT-26 colorectal cancer cells and in a CT-26 tumor-bearing mouse model. Results TKSE suppressed the growth of HT-29 and CT-26 cells (both colorectal cancer cell lines) and the cytotoxic effect of TKSE was greater than that of 5-fluorouracil (5-Fu) in HT-29 cells. TKSE significantly induced mitochondrial membrane potential loss in HT-29 and CT-26 cells and dose-dependently inhibited Bcl-2 expression and induced the cleavages of caspase-3 and PARP. In particular, TKSE at 300 µg/mL induced nuclear condensation and fragmentation in HT-29 cells. Furthermore, TKSE dose-dependently inhibited activations of the Akt/mTOR and ERK pathways, and markedly induced the phosphorylation of AMPK. An AMPKα inhibitor (compound C) effectively blocked the TKSE-induced mitochondrial dysfunction. In addition, TKSE attenuated the hypoxia-inducible factor-1α/vascular endothelial growth factor signaling pathway in HT-29 cells under hypoxic-mimic conditions and inhibited migration and invasion. Oral administration of TKSE (100 or 300 mg/kg) inhibited tumor growth in a mouse CT-26 allograft model but was not as effective as 5-Fu (the positive control), which was administered intraperitoneally. In the same model, 5-Fu caused significant body weight loss, but no such loss was observed in TKSE-treated mice. Conclusion Taken together, these results suggest TKSE has potent anti-tumor effects which might be partly due to the activation of AMPK, and the induction mitochondrial-mediated apoptosis in colorectal cancer cells. These findings provide scientific evidence supporting the potential use of TKSE as a complementary and alternative medicine for the treatment of colorectal cancer. Trichosanthis semen (dpeaa)DE-He213 Colorectal cancer (dpeaa)DE-He213 Anti-cancer (dpeaa)DE-He213 Apoptosis (dpeaa)DE-He213 Anti-tumor (dpeaa)DE-He213 Jeon, Sang Kyu aut Kim, Ok Hyeon aut Ahn, Jung Yun aut Kim, Chang-Hyun aut Park, Sun-Dong aut Lee, Ju-Hee (orcid)0000-0003-4147-9794 aut Enthalten in Chinese medicine London : BioMed Central, 2006 14(2019), 1 vom: 07. Okt. (DE-627)521457025 (DE-600)2260322-0 1749-8546 nnns volume:14 year:2019 number:1 day:07 month:10 https://dx.doi.org/10.1186/s13020-019-0263-8 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 14 2019 1 07 10 |
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10.1186/s13020-019-0263-8 doi (DE-627)SPR02947678X (SPR)s13020-019-0263-8-e DE-627 ger DE-627 rakwb eng Park, Su Mi verfasserin aut Anti-tumor effects of the ethanolic extract of Trichosanthes kirilowii seeds in colorectal cancer 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2019 Background Trichosanthis semen, the seeds of Trichosanthes kirilowii Maxim. or Trichosanthes rosthornii Harms, has long been used in Korean medicine to loosen bowels and relieve chronic constipation. Although the fruits and radixes of this medicinal herb and their constituents have been reported to exhibit therapeutic effects in various cancers, the anti-cancer effects of its seeds have been relatively less studied. In this study, we investigated the effects of an ethanolic extract of T. kirilowii seeds (TKSE) against colorectal cancer and its mechanism. Methods The anti-tumor effects of the TKSE were evaluated in HT-29 and CT-26 colorectal cancer cells and in a CT-26 tumor-bearing mouse model. Results TKSE suppressed the growth of HT-29 and CT-26 cells (both colorectal cancer cell lines) and the cytotoxic effect of TKSE was greater than that of 5-fluorouracil (5-Fu) in HT-29 cells. TKSE significantly induced mitochondrial membrane potential loss in HT-29 and CT-26 cells and dose-dependently inhibited Bcl-2 expression and induced the cleavages of caspase-3 and PARP. In particular, TKSE at 300 µg/mL induced nuclear condensation and fragmentation in HT-29 cells. Furthermore, TKSE dose-dependently inhibited activations of the Akt/mTOR and ERK pathways, and markedly induced the phosphorylation of AMPK. An AMPKα inhibitor (compound C) effectively blocked the TKSE-induced mitochondrial dysfunction. In addition, TKSE attenuated the hypoxia-inducible factor-1α/vascular endothelial growth factor signaling pathway in HT-29 cells under hypoxic-mimic conditions and inhibited migration and invasion. Oral administration of TKSE (100 or 300 mg/kg) inhibited tumor growth in a mouse CT-26 allograft model but was not as effective as 5-Fu (the positive control), which was administered intraperitoneally. In the same model, 5-Fu caused significant body weight loss, but no such loss was observed in TKSE-treated mice. Conclusion Taken together, these results suggest TKSE has potent anti-tumor effects which might be partly due to the activation of AMPK, and the induction mitochondrial-mediated apoptosis in colorectal cancer cells. These findings provide scientific evidence supporting the potential use of TKSE as a complementary and alternative medicine for the treatment of colorectal cancer. Trichosanthis semen (dpeaa)DE-He213 Colorectal cancer (dpeaa)DE-He213 Anti-cancer (dpeaa)DE-He213 Apoptosis (dpeaa)DE-He213 Anti-tumor (dpeaa)DE-He213 Jeon, Sang Kyu aut Kim, Ok Hyeon aut Ahn, Jung Yun aut Kim, Chang-Hyun aut Park, Sun-Dong aut Lee, Ju-Hee (orcid)0000-0003-4147-9794 aut Enthalten in Chinese medicine London : BioMed Central, 2006 14(2019), 1 vom: 07. Okt. (DE-627)521457025 (DE-600)2260322-0 1749-8546 nnns volume:14 year:2019 number:1 day:07 month:10 https://dx.doi.org/10.1186/s13020-019-0263-8 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 14 2019 1 07 10 |
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10.1186/s13020-019-0263-8 doi (DE-627)SPR02947678X (SPR)s13020-019-0263-8-e DE-627 ger DE-627 rakwb eng Park, Su Mi verfasserin aut Anti-tumor effects of the ethanolic extract of Trichosanthes kirilowii seeds in colorectal cancer 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2019 Background Trichosanthis semen, the seeds of Trichosanthes kirilowii Maxim. or Trichosanthes rosthornii Harms, has long been used in Korean medicine to loosen bowels and relieve chronic constipation. Although the fruits and radixes of this medicinal herb and their constituents have been reported to exhibit therapeutic effects in various cancers, the anti-cancer effects of its seeds have been relatively less studied. In this study, we investigated the effects of an ethanolic extract of T. kirilowii seeds (TKSE) against colorectal cancer and its mechanism. Methods The anti-tumor effects of the TKSE were evaluated in HT-29 and CT-26 colorectal cancer cells and in a CT-26 tumor-bearing mouse model. Results TKSE suppressed the growth of HT-29 and CT-26 cells (both colorectal cancer cell lines) and the cytotoxic effect of TKSE was greater than that of 5-fluorouracil (5-Fu) in HT-29 cells. TKSE significantly induced mitochondrial membrane potential loss in HT-29 and CT-26 cells and dose-dependently inhibited Bcl-2 expression and induced the cleavages of caspase-3 and PARP. In particular, TKSE at 300 µg/mL induced nuclear condensation and fragmentation in HT-29 cells. Furthermore, TKSE dose-dependently inhibited activations of the Akt/mTOR and ERK pathways, and markedly induced the phosphorylation of AMPK. An AMPKα inhibitor (compound C) effectively blocked the TKSE-induced mitochondrial dysfunction. In addition, TKSE attenuated the hypoxia-inducible factor-1α/vascular endothelial growth factor signaling pathway in HT-29 cells under hypoxic-mimic conditions and inhibited migration and invasion. Oral administration of TKSE (100 or 300 mg/kg) inhibited tumor growth in a mouse CT-26 allograft model but was not as effective as 5-Fu (the positive control), which was administered intraperitoneally. In the same model, 5-Fu caused significant body weight loss, but no such loss was observed in TKSE-treated mice. Conclusion Taken together, these results suggest TKSE has potent anti-tumor effects which might be partly due to the activation of AMPK, and the induction mitochondrial-mediated apoptosis in colorectal cancer cells. These findings provide scientific evidence supporting the potential use of TKSE as a complementary and alternative medicine for the treatment of colorectal cancer. Trichosanthis semen (dpeaa)DE-He213 Colorectal cancer (dpeaa)DE-He213 Anti-cancer (dpeaa)DE-He213 Apoptosis (dpeaa)DE-He213 Anti-tumor (dpeaa)DE-He213 Jeon, Sang Kyu aut Kim, Ok Hyeon aut Ahn, Jung Yun aut Kim, Chang-Hyun aut Park, Sun-Dong aut Lee, Ju-Hee (orcid)0000-0003-4147-9794 aut Enthalten in Chinese medicine London : BioMed Central, 2006 14(2019), 1 vom: 07. Okt. (DE-627)521457025 (DE-600)2260322-0 1749-8546 nnns volume:14 year:2019 number:1 day:07 month:10 https://dx.doi.org/10.1186/s13020-019-0263-8 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 14 2019 1 07 10 |
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10.1186/s13020-019-0263-8 doi (DE-627)SPR02947678X (SPR)s13020-019-0263-8-e DE-627 ger DE-627 rakwb eng Park, Su Mi verfasserin aut Anti-tumor effects of the ethanolic extract of Trichosanthes kirilowii seeds in colorectal cancer 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2019 Background Trichosanthis semen, the seeds of Trichosanthes kirilowii Maxim. or Trichosanthes rosthornii Harms, has long been used in Korean medicine to loosen bowels and relieve chronic constipation. Although the fruits and radixes of this medicinal herb and their constituents have been reported to exhibit therapeutic effects in various cancers, the anti-cancer effects of its seeds have been relatively less studied. In this study, we investigated the effects of an ethanolic extract of T. kirilowii seeds (TKSE) against colorectal cancer and its mechanism. Methods The anti-tumor effects of the TKSE were evaluated in HT-29 and CT-26 colorectal cancer cells and in a CT-26 tumor-bearing mouse model. Results TKSE suppressed the growth of HT-29 and CT-26 cells (both colorectal cancer cell lines) and the cytotoxic effect of TKSE was greater than that of 5-fluorouracil (5-Fu) in HT-29 cells. TKSE significantly induced mitochondrial membrane potential loss in HT-29 and CT-26 cells and dose-dependently inhibited Bcl-2 expression and induced the cleavages of caspase-3 and PARP. In particular, TKSE at 300 µg/mL induced nuclear condensation and fragmentation in HT-29 cells. Furthermore, TKSE dose-dependently inhibited activations of the Akt/mTOR and ERK pathways, and markedly induced the phosphorylation of AMPK. An AMPKα inhibitor (compound C) effectively blocked the TKSE-induced mitochondrial dysfunction. In addition, TKSE attenuated the hypoxia-inducible factor-1α/vascular endothelial growth factor signaling pathway in HT-29 cells under hypoxic-mimic conditions and inhibited migration and invasion. Oral administration of TKSE (100 or 300 mg/kg) inhibited tumor growth in a mouse CT-26 allograft model but was not as effective as 5-Fu (the positive control), which was administered intraperitoneally. In the same model, 5-Fu caused significant body weight loss, but no such loss was observed in TKSE-treated mice. Conclusion Taken together, these results suggest TKSE has potent anti-tumor effects which might be partly due to the activation of AMPK, and the induction mitochondrial-mediated apoptosis in colorectal cancer cells. These findings provide scientific evidence supporting the potential use of TKSE as a complementary and alternative medicine for the treatment of colorectal cancer. Trichosanthis semen (dpeaa)DE-He213 Colorectal cancer (dpeaa)DE-He213 Anti-cancer (dpeaa)DE-He213 Apoptosis (dpeaa)DE-He213 Anti-tumor (dpeaa)DE-He213 Jeon, Sang Kyu aut Kim, Ok Hyeon aut Ahn, Jung Yun aut Kim, Chang-Hyun aut Park, Sun-Dong aut Lee, Ju-Hee (orcid)0000-0003-4147-9794 aut Enthalten in Chinese medicine London : BioMed Central, 2006 14(2019), 1 vom: 07. Okt. (DE-627)521457025 (DE-600)2260322-0 1749-8546 nnns volume:14 year:2019 number:1 day:07 month:10 https://dx.doi.org/10.1186/s13020-019-0263-8 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 14 2019 1 07 10 |
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Anti-tumor effects of the ethanolic extract of Trichosanthes kirilowii seeds in colorectal cancer |
abstract |
Background Trichosanthis semen, the seeds of Trichosanthes kirilowii Maxim. or Trichosanthes rosthornii Harms, has long been used in Korean medicine to loosen bowels and relieve chronic constipation. Although the fruits and radixes of this medicinal herb and their constituents have been reported to exhibit therapeutic effects in various cancers, the anti-cancer effects of its seeds have been relatively less studied. In this study, we investigated the effects of an ethanolic extract of T. kirilowii seeds (TKSE) against colorectal cancer and its mechanism. Methods The anti-tumor effects of the TKSE were evaluated in HT-29 and CT-26 colorectal cancer cells and in a CT-26 tumor-bearing mouse model. Results TKSE suppressed the growth of HT-29 and CT-26 cells (both colorectal cancer cell lines) and the cytotoxic effect of TKSE was greater than that of 5-fluorouracil (5-Fu) in HT-29 cells. TKSE significantly induced mitochondrial membrane potential loss in HT-29 and CT-26 cells and dose-dependently inhibited Bcl-2 expression and induced the cleavages of caspase-3 and PARP. In particular, TKSE at 300 µg/mL induced nuclear condensation and fragmentation in HT-29 cells. Furthermore, TKSE dose-dependently inhibited activations of the Akt/mTOR and ERK pathways, and markedly induced the phosphorylation of AMPK. An AMPKα inhibitor (compound C) effectively blocked the TKSE-induced mitochondrial dysfunction. In addition, TKSE attenuated the hypoxia-inducible factor-1α/vascular endothelial growth factor signaling pathway in HT-29 cells under hypoxic-mimic conditions and inhibited migration and invasion. Oral administration of TKSE (100 or 300 mg/kg) inhibited tumor growth in a mouse CT-26 allograft model but was not as effective as 5-Fu (the positive control), which was administered intraperitoneally. In the same model, 5-Fu caused significant body weight loss, but no such loss was observed in TKSE-treated mice. Conclusion Taken together, these results suggest TKSE has potent anti-tumor effects which might be partly due to the activation of AMPK, and the induction mitochondrial-mediated apoptosis in colorectal cancer cells. These findings provide scientific evidence supporting the potential use of TKSE as a complementary and alternative medicine for the treatment of colorectal cancer. © The Author(s) 2019 |
abstractGer |
Background Trichosanthis semen, the seeds of Trichosanthes kirilowii Maxim. or Trichosanthes rosthornii Harms, has long been used in Korean medicine to loosen bowels and relieve chronic constipation. Although the fruits and radixes of this medicinal herb and their constituents have been reported to exhibit therapeutic effects in various cancers, the anti-cancer effects of its seeds have been relatively less studied. In this study, we investigated the effects of an ethanolic extract of T. kirilowii seeds (TKSE) against colorectal cancer and its mechanism. Methods The anti-tumor effects of the TKSE were evaluated in HT-29 and CT-26 colorectal cancer cells and in a CT-26 tumor-bearing mouse model. Results TKSE suppressed the growth of HT-29 and CT-26 cells (both colorectal cancer cell lines) and the cytotoxic effect of TKSE was greater than that of 5-fluorouracil (5-Fu) in HT-29 cells. TKSE significantly induced mitochondrial membrane potential loss in HT-29 and CT-26 cells and dose-dependently inhibited Bcl-2 expression and induced the cleavages of caspase-3 and PARP. In particular, TKSE at 300 µg/mL induced nuclear condensation and fragmentation in HT-29 cells. Furthermore, TKSE dose-dependently inhibited activations of the Akt/mTOR and ERK pathways, and markedly induced the phosphorylation of AMPK. An AMPKα inhibitor (compound C) effectively blocked the TKSE-induced mitochondrial dysfunction. In addition, TKSE attenuated the hypoxia-inducible factor-1α/vascular endothelial growth factor signaling pathway in HT-29 cells under hypoxic-mimic conditions and inhibited migration and invasion. Oral administration of TKSE (100 or 300 mg/kg) inhibited tumor growth in a mouse CT-26 allograft model but was not as effective as 5-Fu (the positive control), which was administered intraperitoneally. In the same model, 5-Fu caused significant body weight loss, but no such loss was observed in TKSE-treated mice. Conclusion Taken together, these results suggest TKSE has potent anti-tumor effects which might be partly due to the activation of AMPK, and the induction mitochondrial-mediated apoptosis in colorectal cancer cells. These findings provide scientific evidence supporting the potential use of TKSE as a complementary and alternative medicine for the treatment of colorectal cancer. © The Author(s) 2019 |
abstract_unstemmed |
Background Trichosanthis semen, the seeds of Trichosanthes kirilowii Maxim. or Trichosanthes rosthornii Harms, has long been used in Korean medicine to loosen bowels and relieve chronic constipation. Although the fruits and radixes of this medicinal herb and their constituents have been reported to exhibit therapeutic effects in various cancers, the anti-cancer effects of its seeds have been relatively less studied. In this study, we investigated the effects of an ethanolic extract of T. kirilowii seeds (TKSE) against colorectal cancer and its mechanism. Methods The anti-tumor effects of the TKSE were evaluated in HT-29 and CT-26 colorectal cancer cells and in a CT-26 tumor-bearing mouse model. Results TKSE suppressed the growth of HT-29 and CT-26 cells (both colorectal cancer cell lines) and the cytotoxic effect of TKSE was greater than that of 5-fluorouracil (5-Fu) in HT-29 cells. TKSE significantly induced mitochondrial membrane potential loss in HT-29 and CT-26 cells and dose-dependently inhibited Bcl-2 expression and induced the cleavages of caspase-3 and PARP. In particular, TKSE at 300 µg/mL induced nuclear condensation and fragmentation in HT-29 cells. Furthermore, TKSE dose-dependently inhibited activations of the Akt/mTOR and ERK pathways, and markedly induced the phosphorylation of AMPK. An AMPKα inhibitor (compound C) effectively blocked the TKSE-induced mitochondrial dysfunction. In addition, TKSE attenuated the hypoxia-inducible factor-1α/vascular endothelial growth factor signaling pathway in HT-29 cells under hypoxic-mimic conditions and inhibited migration and invasion. Oral administration of TKSE (100 or 300 mg/kg) inhibited tumor growth in a mouse CT-26 allograft model but was not as effective as 5-Fu (the positive control), which was administered intraperitoneally. In the same model, 5-Fu caused significant body weight loss, but no such loss was observed in TKSE-treated mice. Conclusion Taken together, these results suggest TKSE has potent anti-tumor effects which might be partly due to the activation of AMPK, and the induction mitochondrial-mediated apoptosis in colorectal cancer cells. These findings provide scientific evidence supporting the potential use of TKSE as a complementary and alternative medicine for the treatment of colorectal cancer. © The Author(s) 2019 |
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title_short |
Anti-tumor effects of the ethanolic extract of Trichosanthes kirilowii seeds in colorectal cancer |
url |
https://dx.doi.org/10.1186/s13020-019-0263-8 |
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Jeon, Sang Kyu Kim, Ok Hyeon Ahn, Jung Yun Kim, Chang-Hyun Park, Sun-Dong Lee, Ju-Hee |
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