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http://dx.doi.org/10.7314/APJCP.2016.17.4.2151

Scabraside D Derived from Sea Cucumber Induces Apoptosis and Inhibits Metastasis via iNOS and STAT-3 Expression in Human Cholangiocarcinoma Xenografts  

Assawasuparerk, Kanjana (Preclinic and Applied Animal Science, Faculty of Veterinary Science, Mahidol University)
Rawangchue, Thanakorn (Center for Veterinary Diagnosis, Faculty of Veterinary Science, Mahidol University)
Phonarknguen, Rassameepen (The Monitoring and Surveillance Center for Zoonotic Disease in Wildlife and Exotic Animals, Faculty of Veterinary Science, Mahidol University)
Publication Information
Asian Pacific Journal of Cancer Prevention / v.17, no.4, 2016 , pp. 2151-2157 More about this Journal
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.
Keywords
Scabraside D; sea cucumber; cholangiocarcinoma; apoptosis; metastasis; iNOS; STAT-3;
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