Limits...
In vivo induction of apoptosis by fucoxanthin, a marine carotenoid, associated with down-regulating STAT3/EGFR signaling in sarcoma 180 (S180) xenografts-bearing mice.

Wang J, Chen S, Xu S, Yu X, Ma D, Hu X, Cao X - Mar Drugs (2012)

Bottom Line: But the precise mechanism by which fucoxanthin exerts anticarcinogenic effects is not yet fully understood.In addition, immunohistochemistry analysis and Western blotting analysis showed that fucoxanthin significantly decreased the expressions of survivin and vascular endothelial growth factor (VEGF).Most importantly, fucoxanthin inhibited the expressions of the epidermal growth factor receptor (EGFR) and STAT3 and phosphorylated STAT3 proteins.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacology, College of Medicine, Wuhan University of Science and Technology, Wuhan 430065, China. wangj79@hotmail.com

ABSTRACT
Previous in vitro researches have showed that fucoxanthin, a natural carotenoid isolated from sargassum, can inhibit proliferation or induce apoptosis in human neuroblastoma, hepatoma, leukemia, colon carcinoma, prostate cancer or urinary bladder cancer cells. But the precise mechanism by which fucoxanthin exerts anticarcinogenic effects is not yet fully understood. In this study, we performed an in vivo study to investigate the anti-tumor effect and mechanisms of fucoxanthin on xenografted sarcoma 180 (S180) in mice. Results revealed that fucoxanthin significantly inhibited the growth of sarcoma at the dose of 50 or 100 mg/kg. TUNEL analysis showed that the number of positive cells in the fucoxanthin-treated group was higher than that in the control group. Western blotting analysis also revealed the suppressed expression of bcl-2 and enhanced expression of cleaved caspase-3 by fucoxanthin. In addition, immunohistochemistry analysis and Western blotting analysis showed that fucoxanthin significantly decreased the expressions of survivin and vascular endothelial growth factor (VEGF). Most importantly, fucoxanthin inhibited the expressions of the epidermal growth factor receptor (EGFR) and STAT3 and phosphorylated STAT3 proteins. These results indicated that in vivo induction of apoptosis by fucoxanthin is associated with down-regulating STAT3/EGFR signaling in S180 xenografts-bearing mice.

Show MeSH

Related in: MedlinePlus

Expressions of STAT3 and p-STAT3 proteins in sarcoma tissue (A,B). Western blotting analysis was used to detect the effects of fucoxanthin on the expression of STAT3 and p-STAT3 in S180 tumor tissue. At the presence of fucoxanthin at the dose of 50 or 100 mg/kg body weight, the protein expression of STAT3 (A) and p-STAT3; (B) were reduced than those of the model control group. Values are the mean ± SD. *p < 0.05, **p < 0.01 vs. control group.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC3475273&req=5

marinedrugs-10-02055-f005: Expressions of STAT3 and p-STAT3 proteins in sarcoma tissue (A,B). Western blotting analysis was used to detect the effects of fucoxanthin on the expression of STAT3 and p-STAT3 in S180 tumor tissue. At the presence of fucoxanthin at the dose of 50 or 100 mg/kg body weight, the protein expression of STAT3 (A) and p-STAT3; (B) were reduced than those of the model control group. Values are the mean ± SD. *p < 0.05, **p < 0.01 vs. control group.

Mentions: It was reported that survivin and VEGF expressions are both upregulated primarily by activation of STAT3 signaling, which were known as STAT3-survivin signaling pathway [32] and STAT3-mediated VEGF pathway [23,35], respectively. STAT3 is an important member of the STAT family as DNA binding protein. The continuous activation of STAT3 can induce proliferation, differentiation, closely related genes high expression, thus promoting cell proliferation, malignant transformation, blocking cell apoptosis, displaying a strong effect that causes cancer [36]. At present, many STAT3 target genes have been identified including antiapoptotic gene bcl-xl, bcl-2, mcl-1, cyclin D, c-Myc, MMPs, survivin and VEGF [37]. Previous researches have proven that fucoxanthin down-regulated bcl-xl [13] and cyclin D [10,18]. In this research, we found fucoxanthin treatment groups inhibited the expressions of bcl-2, survivin and VEGF. Since these STAT3 target genes all are influenced by fucoxanthin, we raised up a question: could fucoxanthin regulate STAT3 expression in S180 tumor? To address this item, we focused our attention on STAT3 and its phosphorylation protein level. As expected, fucoxanthin decreased the expression of STAT3 and phosphorylated STAT3 (p-STAT3), which was consistent with our in vitro result [19]. At the presence of CTX and fucoxanthin at the dose of 50 or 100 mg/kg body weight, the protein expression of STAT3 (Figure 5A) and p-STAT3 (Figure 5B) were reduced than those of the model control group (p < 0.05 and p < 0.01, respectively), all these effects of fucoxanthin being presented in a dose-dependent manner.


In vivo induction of apoptosis by fucoxanthin, a marine carotenoid, associated with down-regulating STAT3/EGFR signaling in sarcoma 180 (S180) xenografts-bearing mice.

Wang J, Chen S, Xu S, Yu X, Ma D, Hu X, Cao X - Mar Drugs (2012)

Expressions of STAT3 and p-STAT3 proteins in sarcoma tissue (A,B). Western blotting analysis was used to detect the effects of fucoxanthin on the expression of STAT3 and p-STAT3 in S180 tumor tissue. At the presence of fucoxanthin at the dose of 50 or 100 mg/kg body weight, the protein expression of STAT3 (A) and p-STAT3; (B) were reduced than those of the model control group. Values are the mean ± SD. *p < 0.05, **p < 0.01 vs. control group.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3475273&req=5

marinedrugs-10-02055-f005: Expressions of STAT3 and p-STAT3 proteins in sarcoma tissue (A,B). Western blotting analysis was used to detect the effects of fucoxanthin on the expression of STAT3 and p-STAT3 in S180 tumor tissue. At the presence of fucoxanthin at the dose of 50 or 100 mg/kg body weight, the protein expression of STAT3 (A) and p-STAT3; (B) were reduced than those of the model control group. Values are the mean ± SD. *p < 0.05, **p < 0.01 vs. control group.
Mentions: It was reported that survivin and VEGF expressions are both upregulated primarily by activation of STAT3 signaling, which were known as STAT3-survivin signaling pathway [32] and STAT3-mediated VEGF pathway [23,35], respectively. STAT3 is an important member of the STAT family as DNA binding protein. The continuous activation of STAT3 can induce proliferation, differentiation, closely related genes high expression, thus promoting cell proliferation, malignant transformation, blocking cell apoptosis, displaying a strong effect that causes cancer [36]. At present, many STAT3 target genes have been identified including antiapoptotic gene bcl-xl, bcl-2, mcl-1, cyclin D, c-Myc, MMPs, survivin and VEGF [37]. Previous researches have proven that fucoxanthin down-regulated bcl-xl [13] and cyclin D [10,18]. In this research, we found fucoxanthin treatment groups inhibited the expressions of bcl-2, survivin and VEGF. Since these STAT3 target genes all are influenced by fucoxanthin, we raised up a question: could fucoxanthin regulate STAT3 expression in S180 tumor? To address this item, we focused our attention on STAT3 and its phosphorylation protein level. As expected, fucoxanthin decreased the expression of STAT3 and phosphorylated STAT3 (p-STAT3), which was consistent with our in vitro result [19]. At the presence of CTX and fucoxanthin at the dose of 50 or 100 mg/kg body weight, the protein expression of STAT3 (Figure 5A) and p-STAT3 (Figure 5B) were reduced than those of the model control group (p < 0.05 and p < 0.01, respectively), all these effects of fucoxanthin being presented in a dose-dependent manner.

Bottom Line: But the precise mechanism by which fucoxanthin exerts anticarcinogenic effects is not yet fully understood.In addition, immunohistochemistry analysis and Western blotting analysis showed that fucoxanthin significantly decreased the expressions of survivin and vascular endothelial growth factor (VEGF).Most importantly, fucoxanthin inhibited the expressions of the epidermal growth factor receptor (EGFR) and STAT3 and phosphorylated STAT3 proteins.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacology, College of Medicine, Wuhan University of Science and Technology, Wuhan 430065, China. wangj79@hotmail.com

ABSTRACT
Previous in vitro researches have showed that fucoxanthin, a natural carotenoid isolated from sargassum, can inhibit proliferation or induce apoptosis in human neuroblastoma, hepatoma, leukemia, colon carcinoma, prostate cancer or urinary bladder cancer cells. But the precise mechanism by which fucoxanthin exerts anticarcinogenic effects is not yet fully understood. In this study, we performed an in vivo study to investigate the anti-tumor effect and mechanisms of fucoxanthin on xenografted sarcoma 180 (S180) in mice. Results revealed that fucoxanthin significantly inhibited the growth of sarcoma at the dose of 50 or 100 mg/kg. TUNEL analysis showed that the number of positive cells in the fucoxanthin-treated group was higher than that in the control group. Western blotting analysis also revealed the suppressed expression of bcl-2 and enhanced expression of cleaved caspase-3 by fucoxanthin. In addition, immunohistochemistry analysis and Western blotting analysis showed that fucoxanthin significantly decreased the expressions of survivin and vascular endothelial growth factor (VEGF). Most importantly, fucoxanthin inhibited the expressions of the epidermal growth factor receptor (EGFR) and STAT3 and phosphorylated STAT3 proteins. These results indicated that in vivo induction of apoptosis by fucoxanthin is associated with down-regulating STAT3/EGFR signaling in S180 xenografts-bearing mice.

Show MeSH
Related in: MedlinePlus