Publication: Scabraside D derived from sea cucumber induces apoptosis and inhibits metastasis via iNOS and STAT-3 expression in human cholangiocarcinoma xenografts
Issued Date
2016-01-01
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ISSN
15137368
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2-s2.0-84973163724
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Mahidol University
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SCOPUS
Bibliographic Citation
Asian Pacific Journal of Cancer Prevention. Vol.17, No.4 (2016), 2151-2157
Suggested Citation
Kanjana Assawasuparerk, Thanakorn Rawangchue, Rassameepen Phonarknguen Scabraside D derived from sea cucumber induces apoptosis and inhibits metastasis via iNOS and STAT-3 expression in human cholangiocarcinoma xenografts. Asian Pacific Journal of Cancer Prevention. Vol.17, No.4 (2016), 2151-2157. doi:10.7314/APJCP.2016.17.4.2151 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/43148
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Title
Scabraside D derived from sea cucumber induces apoptosis and inhibits metastasis via iNOS and STAT-3 expression in human cholangiocarcinoma xenografts
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Abstract
Scabraside D, a sulfated triterpene glycoside, was extracted from the sea cucumber Holothuria scabra. It shows anti-proliferation in many of cancer cell lines, but the function and mechanisms of action of scabraside D in human cholangiocarcinoma (HuCCA) have not previously determined. In this study, we investigated the activity of scabraside D on HuCCA cell apoptosis, lymphangiogenesis and metastasis in a nude mouse model. Scabraside D induced signs of apoptosis, such as cell shrinkage, nuclear condensation, nuclear fragmentation and DNA fragmentation on TUNEL assays, while effectively decreasing expression of BCl-2 but increasing caspase-3 gene level expression. Immunohistochemistry revealed that scabraside D significantly reduced lymphatic vessel density (LVD). Moreover, scabraside D treatment significantly decreased VEGF-C, MMP-9 and uPA gene expression, which play important roles in the lymphangiogenesis and invasion of cancer cells in metastasis processes. Quantitative real-time PCR showed that scabraside D significantly decreased iNOS and STAT-3 gene expression. This study demonstrated that scabraside D plays a role in activation of HuCCA tumor apoptosis and inhibition of lymphangiogenesis, invasion and metastasis through decreasing BCl-2, MMP-9, uPA and VEGF-C and increasing caspase-3 expression by suppression of iNOS and STAT-3 expression. Therefore, scabraside D could be a promising candidate for cholangiocarcinoma treatment.