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

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.

• Authors: Jun Wang, Shihui Chen, Shiqiang Xu, Xing Yu, Dongqing Ma, Xiamin Hu, Xiaolu Cao
• Journal: Marine drugs (Mar Drugs) Vol. 10 Issue 9 Pg. 2055-2068 (Sep 2012) ISSN: 1660-3397 [Electronic] Switzerland
• PMID: 23118721 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Birc5 protein, mouse
• Inhibitor of Apoptosis Proteins
• Proto-Oncogene Proteins c-bcl-2
• Repressor Proteins
• STAT3 Transcription Factor
• Stat3 protein, mouse
• Survivin
• Vascular Endothelial Growth Factor A
• Xanthophylls
• vascular endothelial growth factor A, mouse
• fucoxanthin
• Carotenoids
• EGFR protein, mouse
• ErbB Receptors
• Caspase 3

Topics

• Animals
• Antineoplastic Agents (pharmacology)
• Apoptosis (drug effects, genetics)
• Carotenoids (pharmacology)
• Caspase 3 (genetics, metabolism)
• Down-Regulation (drug effects)
• ErbB Receptors (genetics, metabolism)
• Inhibitor of Apoptosis Proteins (genetics, metabolism)
• Male
• Mice
• Proto-Oncogene Proteins c-bcl-2 (genetics, metabolism)
• Repressor Proteins (genetics, metabolism)
• STAT3 Transcription Factor (genetics, metabolism)
• Sarcoma 180 (drug therapy, genetics, metabolism)
• Signal Transduction (drug effects)
• Survivin
• Transplantation, Heterologous
• Vascular Endothelial Growth Factor A (genetics, metabolism)
• Xanthophylls (pharmacology)