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Sanguisorba officinalis L synergistically enhanced 5-fluorouracil cytotoxicity in colorectal cancer cells by promoting a reactive oxygen species-mediated, mitochondria-caspase-dependent apoptotic pathway

View Article: PubMed Central - PubMed

ABSTRACT

Sanguisorba officinalis L. radix is a widely used herb called DiYu (DY) in China and has an extensive range of bioactivities, including anti-cancer, anti-inflammatory, and anti-oxidative activities. However, there is little evidence to support its anti-cancer effects against colorectal cancer (CRC). The first-line chemotherapeutic agent 5-fluorouracil (5-FU) is used to treat CRC, but its efficiency is hampered by acquired drug resistance. This study found that a water extract of DY exerted anti-proliferative effects against two CRC cell lines (HCT-116 and RKO), and it sensitized CRC cells to 5-FU therapy by activating a reactive oxygen species (ROS)-mediated, mitochondria-caspase-dependent apoptotic pathway. Co-treatment of DY and 5-FU significantly elevated ROS levels, up-regulated Bax/Bcl-2 ratio and triggered mitochondrial dysfunction, followed by a release of cytochrome c and up-regulation of proteins such as cleaved-caspase-9/3 and cleaved-PARP. Additionally, the induction of autophagy may be involved in mediating synergism of DY in HCT-116 cells. Gallic acid (GA), catechinic acid (CA) and ellagic acid (EA) were identified as the potential chief constituents responsible for the synergistic effects of DY. In conclusion, co-treatment of DY, specifically GA, CA and EA, with 5-FU may be a potential alternative therapeutic strategy for CRC by enhancing an intrinsic apoptotic pathway.

No MeSH data available.


DY exhibited anti-proliferation effects against CRC cells and sensitized them to the cytotoxicity of 5-FU.(a) Cells were treated with DY extracts (12.5–400 μg/ml) for 24 or 48 h, CCK8 assay was then performed to evaluate the cell viability. (b) Cells were separately incubated with DY (100 μg/ml) or 5-FU (20 μM, HCT-116; 5 μM, RKO) and their combination for 24 or 48 h and cell viabilities were assessed by CCK8 assay. *P < 0.05, **P < 0.01, ***P < 0.001, compared with (DY + 5-FU) group. Results are expressed as mean ± SD (n = 3). (c) Cellular morphologies of CRC cells with 48 h treatments as described in (b) were observed under inverted microscope (400×).
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f1: DY exhibited anti-proliferation effects against CRC cells and sensitized them to the cytotoxicity of 5-FU.(a) Cells were treated with DY extracts (12.5–400 μg/ml) for 24 or 48 h, CCK8 assay was then performed to evaluate the cell viability. (b) Cells were separately incubated with DY (100 μg/ml) or 5-FU (20 μM, HCT-116; 5 μM, RKO) and their combination for 24 or 48 h and cell viabilities were assessed by CCK8 assay. *P < 0.05, **P < 0.01, ***P < 0.001, compared with (DY + 5-FU) group. Results are expressed as mean ± SD (n = 3). (c) Cellular morphologies of CRC cells with 48 h treatments as described in (b) were observed under inverted microscope (400×).

Mentions: To assess the cytotoxicity of DY in CRC cells, the cell viabilities of two CRC cell lines treated with DY extracts were determined. IC50 values of DY at 48 h in HCT-116 and RKO cells were 123.92 ± 46.92 μg/ml and 120.43 ± 26.59 μg/ml (IC50 < 200 μg/ml), respectively. While DY showed low cytotoxicity, with an IC50 of 255.70 ± 44.12 μg/ml, towards NCM460 cells (a normal human colorectal mucosal epithelial cell line) (Fig. 1a). Notably, the data indicate that DY had anti-proliferative activities towards two CRC cell lines.


Sanguisorba officinalis L synergistically enhanced 5-fluorouracil cytotoxicity in colorectal cancer cells by promoting a reactive oxygen species-mediated, mitochondria-caspase-dependent apoptotic pathway
DY exhibited anti-proliferation effects against CRC cells and sensitized them to the cytotoxicity of 5-FU.(a) Cells were treated with DY extracts (12.5–400 μg/ml) for 24 or 48 h, CCK8 assay was then performed to evaluate the cell viability. (b) Cells were separately incubated with DY (100 μg/ml) or 5-FU (20 μM, HCT-116; 5 μM, RKO) and their combination for 24 or 48 h and cell viabilities were assessed by CCK8 assay. *P < 0.05, **P < 0.01, ***P < 0.001, compared with (DY + 5-FU) group. Results are expressed as mean ± SD (n = 3). (c) Cellular morphologies of CRC cells with 48 h treatments as described in (b) were observed under inverted microscope (400×).
© Copyright Policy - open-access
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC5037464&req=5

f1: DY exhibited anti-proliferation effects against CRC cells and sensitized them to the cytotoxicity of 5-FU.(a) Cells were treated with DY extracts (12.5–400 μg/ml) for 24 or 48 h, CCK8 assay was then performed to evaluate the cell viability. (b) Cells were separately incubated with DY (100 μg/ml) or 5-FU (20 μM, HCT-116; 5 μM, RKO) and their combination for 24 or 48 h and cell viabilities were assessed by CCK8 assay. *P < 0.05, **P < 0.01, ***P < 0.001, compared with (DY + 5-FU) group. Results are expressed as mean ± SD (n = 3). (c) Cellular morphologies of CRC cells with 48 h treatments as described in (b) were observed under inverted microscope (400×).
Mentions: To assess the cytotoxicity of DY in CRC cells, the cell viabilities of two CRC cell lines treated with DY extracts were determined. IC50 values of DY at 48 h in HCT-116 and RKO cells were 123.92 ± 46.92 μg/ml and 120.43 ± 26.59 μg/ml (IC50 < 200 μg/ml), respectively. While DY showed low cytotoxicity, with an IC50 of 255.70 ± 44.12 μg/ml, towards NCM460 cells (a normal human colorectal mucosal epithelial cell line) (Fig. 1a). Notably, the data indicate that DY had anti-proliferative activities towards two CRC cell lines.

View Article: PubMed Central - PubMed

ABSTRACT

Sanguisorba officinalis L. radix is a widely used herb called DiYu (DY) in China and has an extensive range of bioactivities, including anti-cancer, anti-inflammatory, and anti-oxidative activities. However, there is little evidence to support its anti-cancer effects against colorectal cancer (CRC). The first-line chemotherapeutic agent 5-fluorouracil (5-FU) is used to treat CRC, but its efficiency is hampered by acquired drug resistance. This study found that a water extract of DY exerted anti-proliferative effects against two CRC cell lines (HCT-116 and RKO), and it sensitized CRC cells to 5-FU therapy by activating a reactive oxygen species (ROS)-mediated, mitochondria-caspase-dependent apoptotic pathway. Co-treatment of DY and 5-FU significantly elevated ROS levels, up-regulated Bax/Bcl-2 ratio and triggered mitochondrial dysfunction, followed by a release of cytochrome c and up-regulation of proteins such as cleaved-caspase-9/3 and cleaved-PARP. Additionally, the induction of autophagy may be involved in mediating synergism of DY in HCT-116 cells. Gallic acid (GA), catechinic acid (CA) and ellagic acid (EA) were identified as the potential chief constituents responsible for the synergistic effects of DY. In conclusion, co-treatment of DY, specifically GA, CA and EA, with 5-FU may be a potential alternative therapeutic strategy for CRC by enhancing an intrinsic apoptotic pathway.

No MeSH data available.