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Ethanol extract of Forsythia suspensa root induces apoptosis of esophageal carcinoma cells via the mitochondrial apoptotic pathway.

Zhao L, Yan X, Shi J, Ren F, Liu L, Sun S, Shan B - Mol Med Rep (2014)

Bottom Line: The results revealed that FSREE, rather than Forsythia suspensa ethanolic extracts from the leaf (FSLEE) and fruit (FSFEE) exhibited marked anti-tumor activity towards human esophageal cancer cells.FSREE induced cancer cell apoptosis and growth arrest by downregulating B‑cell lymphoma (Bcl)‑2, Bcl‑extra large and myeloid cell leukemia 1, while upregulating Bcl‑2‑associated X protein, Bcl‑2 antagonist of cell death and phorbol‑12‑myristate‑13‑acetate‑induced protein 1.Furthermore, the anti-cancer activity of FSREE was associated with a decreased level of phosphorylated Janus kinase/signal transducer and activator of transcription 3 and extracellular‑signal‑regulated kinase signaling activity.

View Article: PubMed Central - PubMed

Affiliation: Research Center, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei 050011, P.R. China.

ABSTRACT
Forsythia suspensa root is used in the treatment of fever and jaundice in Traditional Chinese Medicine. In the present study, the anti-tumor activity of the ethanolic extract of Forsythia suspensa root (FSREE) against esophageal carcinoma cells was investigated in vitro and in vivo and its anti-cancer mechanism was examined. The results revealed that FSREE, rather than Forsythia suspensa ethanolic extracts from the leaf (FSLEE) and fruit (FSFEE) exhibited marked anti-tumor activity towards human esophageal cancer cells. FSREE induced cancer cell apoptosis and growth arrest by downregulating B‑cell lymphoma (Bcl)‑2, Bcl‑extra large and myeloid cell leukemia 1, while upregulating Bcl‑2‑associated X protein, Bcl‑2 antagonist of cell death and phorbol‑12‑myristate‑13‑acetate‑induced protein 1. This led to the activation of poly(ADP ribose) polymerase, caspase‑3 and caspase‑9, but not caspase‑8. Furthermore, the anti-cancer activity of FSREE was associated with a decreased level of phosphorylated Janus kinase/signal transducer and activator of transcription 3 and extracellular‑signal‑regulated kinase signaling activity. It was also observed that the levels of cytochrome c were elevated in the cytoplasm, accounting for the loss of mitochondrial membrane potential in the TE‑13 cells upon treatment with FSEER. In addition, FSEER inhibited the growth of esophageal cancer cells in xenograft models and no detectable toxicity was present in the lung or liver tissues. These observations provided further evidence of the anti-tumor effect of FSEER and may be of importance to further examine the potential role of Forsythia suspensa root as a therapeutic agent in esophageal carcinoma therapy.

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FSEER mediates the inhibition of tumor growth in vivo. TE13 xenograft mice were treated intraperitoneally with PBS or FSEER (50 mg/kg) once every two days for 14 days. (A) Two representative athymic nude mice from the PBS-treated and FSEER (50 mg/kg)-treated groups. (B and C) Antitumor efficacy of FSEER in the TE-13 xenograft model. Values are expressed as the mean ±standard deviation (n=5). (D) Tissues from the liver and lung of the tumor xenograft mice were stained using hematoxylin and eosin. *P<0.05, **P<0.01, compared with the control group. FSEER, Forsythia suspensa ethanolic extract of the root; PBS, phosphate-buffered saline.
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f6-mmr-11-02-0871: FSEER mediates the inhibition of tumor growth in vivo. TE13 xenograft mice were treated intraperitoneally with PBS or FSEER (50 mg/kg) once every two days for 14 days. (A) Two representative athymic nude mice from the PBS-treated and FSEER (50 mg/kg)-treated groups. (B and C) Antitumor efficacy of FSEER in the TE-13 xenograft model. Values are expressed as the mean ±standard deviation (n=5). (D) Tissues from the liver and lung of the tumor xenograft mice were stained using hematoxylin and eosin. *P<0.05, **P<0.01, compared with the control group. FSEER, Forsythia suspensa ethanolic extract of the root; PBS, phosphate-buffered saline.

Mentions: The established TE-13 cells implanted into nude mice were used as a model to observe the effect of FSEER on the tumor burden in vivo. The treatment regimens were performed as described previously. As shown in Fig. 6A, compared with the control group, the FSEER-treated group demonstrated significant inhibition of tumor growth. Following treatment with FSEER for 20 days, the mean tumor volume of the treated group was 0.79+0.17 cm3 and the mean weight was 0.35+0.08 mg. These were significantly lower compared with those of the control group, which were 2.56+0.18 cm3 and 1.35+0.11 mg, respectively (Fig. 6B) Following inoculation of the TE-13 cells, a clear increase in tumor volume was observed from day 7 in the vehicle group until the animals were sacrificed. However, tumor volume in mice treated with FSEER (50 mg/ml) from the day of inoculation started to increase from day 10 and tumor volume increased slowly (Fig. 6C). Furthermore, no clear pathological changes were observed in the liver and lung in the H&E-stained sections of FSEER-treated mice (Fig. 6D), indicating that FSEER had no detectable toxicity in mice. In conclusion, these results indicated that FSEER exerted anti-tumor effect in vitro and in vivo.


Ethanol extract of Forsythia suspensa root induces apoptosis of esophageal carcinoma cells via the mitochondrial apoptotic pathway.

Zhao L, Yan X, Shi J, Ren F, Liu L, Sun S, Shan B - Mol Med Rep (2014)

FSEER mediates the inhibition of tumor growth in vivo. TE13 xenograft mice were treated intraperitoneally with PBS or FSEER (50 mg/kg) once every two days for 14 days. (A) Two representative athymic nude mice from the PBS-treated and FSEER (50 mg/kg)-treated groups. (B and C) Antitumor efficacy of FSEER in the TE-13 xenograft model. Values are expressed as the mean ±standard deviation (n=5). (D) Tissues from the liver and lung of the tumor xenograft mice were stained using hematoxylin and eosin. *P<0.05, **P<0.01, compared with the control group. FSEER, Forsythia suspensa ethanolic extract of the root; PBS, phosphate-buffered saline.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4262507&req=5

f6-mmr-11-02-0871: FSEER mediates the inhibition of tumor growth in vivo. TE13 xenograft mice were treated intraperitoneally with PBS or FSEER (50 mg/kg) once every two days for 14 days. (A) Two representative athymic nude mice from the PBS-treated and FSEER (50 mg/kg)-treated groups. (B and C) Antitumor efficacy of FSEER in the TE-13 xenograft model. Values are expressed as the mean ±standard deviation (n=5). (D) Tissues from the liver and lung of the tumor xenograft mice were stained using hematoxylin and eosin. *P<0.05, **P<0.01, compared with the control group. FSEER, Forsythia suspensa ethanolic extract of the root; PBS, phosphate-buffered saline.
Mentions: The established TE-13 cells implanted into nude mice were used as a model to observe the effect of FSEER on the tumor burden in vivo. The treatment regimens were performed as described previously. As shown in Fig. 6A, compared with the control group, the FSEER-treated group demonstrated significant inhibition of tumor growth. Following treatment with FSEER for 20 days, the mean tumor volume of the treated group was 0.79+0.17 cm3 and the mean weight was 0.35+0.08 mg. These were significantly lower compared with those of the control group, which were 2.56+0.18 cm3 and 1.35+0.11 mg, respectively (Fig. 6B) Following inoculation of the TE-13 cells, a clear increase in tumor volume was observed from day 7 in the vehicle group until the animals were sacrificed. However, tumor volume in mice treated with FSEER (50 mg/ml) from the day of inoculation started to increase from day 10 and tumor volume increased slowly (Fig. 6C). Furthermore, no clear pathological changes were observed in the liver and lung in the H&E-stained sections of FSEER-treated mice (Fig. 6D), indicating that FSEER had no detectable toxicity in mice. In conclusion, these results indicated that FSEER exerted anti-tumor effect in vitro and in vivo.

Bottom Line: The results revealed that FSREE, rather than Forsythia suspensa ethanolic extracts from the leaf (FSLEE) and fruit (FSFEE) exhibited marked anti-tumor activity towards human esophageal cancer cells.FSREE induced cancer cell apoptosis and growth arrest by downregulating B‑cell lymphoma (Bcl)‑2, Bcl‑extra large and myeloid cell leukemia 1, while upregulating Bcl‑2‑associated X protein, Bcl‑2 antagonist of cell death and phorbol‑12‑myristate‑13‑acetate‑induced protein 1.Furthermore, the anti-cancer activity of FSREE was associated with a decreased level of phosphorylated Janus kinase/signal transducer and activator of transcription 3 and extracellular‑signal‑regulated kinase signaling activity.

View Article: PubMed Central - PubMed

Affiliation: Research Center, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei 050011, P.R. China.

ABSTRACT
Forsythia suspensa root is used in the treatment of fever and jaundice in Traditional Chinese Medicine. In the present study, the anti-tumor activity of the ethanolic extract of Forsythia suspensa root (FSREE) against esophageal carcinoma cells was investigated in vitro and in vivo and its anti-cancer mechanism was examined. The results revealed that FSREE, rather than Forsythia suspensa ethanolic extracts from the leaf (FSLEE) and fruit (FSFEE) exhibited marked anti-tumor activity towards human esophageal cancer cells. FSREE induced cancer cell apoptosis and growth arrest by downregulating B‑cell lymphoma (Bcl)‑2, Bcl‑extra large and myeloid cell leukemia 1, while upregulating Bcl‑2‑associated X protein, Bcl‑2 antagonist of cell death and phorbol‑12‑myristate‑13‑acetate‑induced protein 1. This led to the activation of poly(ADP ribose) polymerase, caspase‑3 and caspase‑9, but not caspase‑8. Furthermore, the anti-cancer activity of FSREE was associated with a decreased level of phosphorylated Janus kinase/signal transducer and activator of transcription 3 and extracellular‑signal‑regulated kinase signaling activity. It was also observed that the levels of cytochrome c were elevated in the cytoplasm, accounting for the loss of mitochondrial membrane potential in the TE‑13 cells upon treatment with FSEER. In addition, FSEER inhibited the growth of esophageal cancer cells in xenograft models and no detectable toxicity was present in the lung or liver tissues. These observations provided further evidence of the anti-tumor effect of FSEER and may be of importance to further examine the potential role of Forsythia suspensa root as a therapeutic agent in esophageal carcinoma therapy.

Show MeSH
Related in: MedlinePlus