Advanced SearchSearch Tips
Scabraside D Extracted from Holothuria scabra Induces Apoptosis and Inhibits Growth of Human Cholangiocarcinoma Xenografts in Mice
facebook(new window)  Pirnt(new window) E-mail(new window) Excel Download
 Title & Authors
Scabraside D Extracted from Holothuria scabra Induces Apoptosis and Inhibits Growth of Human Cholangiocarcinoma Xenografts in Mice
Assawasuparerk, Kanjana; Vanichviriyakit, Rapeepun; Chotwiwatthanakun, Charoonroj; Nobsathian, Saksit; Rawangchue, Thanakorn; Wittayachumnankul, Boonsirm;
  PDF(new window)
Scabraside D, a sulfated triterpene glycoside extract from sea cucumber Holothulia scabra, shows various biological activities, but effects on human cholangiocarcinoma cells have not previously been reported. In the present study, we investigated the activity of scabraside D against human cholangiocarcinoma (HuCCA) both in vitro and for tumor growth inhibition in vivo using a xenograft model in nude mice. Scabraside D () significantly decreased the viability and the migration of the HuCCA cells in a dose-dependent manner, with 50% inhibitory concentration (IC50) of at 24 h. It induced signs of apoptotic cells, including shrinkage, pyknosis and karyorrhetic nuclei and DNA fragmentation on agarose gel electrophoresis. Moreover, by quantitative real-time PCR, scabraside D effectively decreased Bcl-2 while increasing Bax and Caspase-3 gene expression levels suggesting that the scabraside D could induce apoptosis in HuCCA cells. In vivo study demonstrated that scabraside D (1 mg/kg/day, i.p. for 21 days) significantly reduced growth of the HuCCA xenografts without adverse effects on the nude mice. Conclusively, scabraside D induced apoptosis in HuCCA cells and reduced the growth of HuCCA xenographs model. Therefore, scabraside D may have potential as a new therapeutic agent for cholangiocarcinoma.
Scabraside D;Holothuria scabra;cholangiocarcinoma;apoptosis;sea cucumber extract;
 Cited by
An antioxidant activity of the whole body of Holothuria scabra, Chemical and Biological Technologies in Agriculture, 2017, 4, 1  crossref(new windwow)
Adrain TE (2007). Novel marine-derived anti-cancer agents. Curr Pharm Des, 13, 3417-26. crossref(new window)

Bahrami Y, Zhang W, Chataway T, et al (2014). Structural elucidation of novel saponins in the sea cucumber Holothuria lessoni. Mar Drugs, 12, 4439-73. crossref(new window)

Bhattarai G, Lee YH, Lee IK, et al (2012). Fomitoside-K from Fomitopsis nigra induces apoptosis of human oral squamous cell carcinomas (YD-10B) via mitochondrial signaling. Biol Pharma Bull, 35, 1711-19. crossref(new window)

Bras M, Queenan B, Susin SA (2005). Programmed cell death via mitochondria: different modes of dying. Biochem (Mosc), 70, 231-39. crossref(new window)

Camins A, Pallas M, Silvestre JS (2008) Apoptotic mechanisms involved in Neurodegenerative diseases: experimental and therapeutic approaches. Method Find Exp Clin Pharmacol, 30, 43-65. crossref(new window)

Caulier G, Dyck SV, Gerbaux P, et al (2011). Review of saponin diversity in sea cucumbers belonging to the family Holothuriidae. SPC Beche-de-mer Inf Bull, 31, 48-54.

Chen X, Li Y, Lin Q, et al (2014). Tea polyphenols induced apoptosis of breast cancer cells by suppressing the expression of Survivin. Sci Rep, 4, 1-5.

Chludil HD, Muniain CC, Seldes AM, et al (2002). Cytotoxic and antifungal triterpene glycosides from the Patagonian sea cucumber Hemoiedema spectabilis. J Nat Prod, 65, 860-65. crossref(new window)

Green DR, Reed JC (1998). Mitochondria and apoptosis. Science, 281, 1309-12. crossref(new window)

Han H, Li L, Yi YH, et al (2012). Triterpene glycosides from sea cucumber Holothuria scabra with cytotoxic activity. Chin Herb Med, 4, 183-88.

Haswell-Elkins MR, Mairiang E, Mairiang P, et al (1994). Cross-sectional study of opisthorchis viverrini infection and cholangiocarcinoma in communities within a high-risk area in northeast Thailand. Int J Cancer, 59, 505-9. crossref(new window)

Hejna M, Pruckmayer M, Raderer M (1998). The role of chemotherapy and radiation in the management of biliary cancer: a review of the literature. Eur J Cancer, 34, 977-86. crossref(new window)

Kerr RG, Chen Z (1995). In vivo and in vitro biosynthesis of saponins in sea cucumbers. J Nat Prod, 58, 172-76. crossref(new window)

Kitagawa I, Kobayashi M, Hori M, et al (1989). Marine natural products. XVIII. Four lanostane-type triterpene oligoglycosides, bivittosides A, B, C, and D, from the Okinawan sea cucumber Bohadschia bivittata Mitsukuri. Chem Pharma Bull, 37, 61-7. crossref(new window)

Li X, Roginsky AB, Ding XZ, et al (2008). Review of the apoptosis pathways in pancreatic cancer and the antiapoptotic effect of the novel sea cucumber compound, Frondoside A. Ann N Y Acad Sci, 1138, 181-98. crossref(new window)

Liang CC, Park AY, Guan JL (2007). In vitro scratch assay: a convenient and inexpensive method for analysis of cell migration in vitro. Nat Protc, 2, 329-33. crossref(new window)

Mark MC (1992). Abiochemical hallmark of apoptosis: internucleosomal degradation of the genome. Canc Metastasis Rev, 11, 105-19. crossref(new window)

Mosmann T (1983). Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods, 65, 55-63. crossref(new window)

Oltersdorf T, Elmore SW, Shoemaker AR, et al (2005). An inhibitor of Bcl-2 family proteins induces regression of solid tumors. Nature, 435, 677-81. crossref(new window)

Piotr D, Dumanska M, Forgacz J, et al (2004). Intensity of apoptosis as related to the expression of metallothionein (MT), caspase-3 (cas-3) and Ki-67 antigen and the survival time of patients with primary colorectal adenocarcinomas. Ocz Akad Med Bialymst, 49, 5-7.

Plengsuriyakarn T, Viyanant V, Eursitthichai V, et al (2012). Anticancer activities against cholangiocarcinoma, toxicity and pharmacological activities of Thai medicinal plants in animal models. BMC Complement Altern Med, 12, 1-19. crossref(new window)

Rajasekaran A, Sivagnanam G, Xavier R (2008). Nutraceuticals as therapeutic agents: a review research. J Pharm Tech, 1, 328-40.

Shin HR, Oh JK, Masuyer E, et al (2010). Epidemiology of cholangiocarcinoma: an update focusing on risk factors. Cancer Sci, 101, 579-85. crossref(new window)

Sirica AE (2005). Cholangiocarcinoma: molecular targeting strategies for chemoprevention and therapy. Hepatol, 41, 5-15. crossref(new window)

Sripa B, Bethony JM, Sithithaworn P, et al (2011). Opisthoriasis and Opisthorchis-associated cholangiocarcinoma in Thailand and Laos. Acta Trop, 120, 158-68. crossref(new window)

Sripa B, Pairojkul C (2008). Cholangiocarcinoma: lessons from Thailand. Curr Opin Gastroenterol, 24, 349-56. crossref(new window)

Stonix VA, Kalinin VI, Avilov SA (1999). Toxin from sea cucumbers (Holothuroids): chemical structures, properties, taxonomic distribution, biosynthesis and evolution. J Nat Toxins, 8, 235-48.

Tada H, Shiho O, Kuroshima M, et al (1986). An improved colorimetric assay for interleukin 2. J Immunol Methods, 93, 157-65. crossref(new window)

Tian F, Zhang X, Tong Y, et al (2005). PE, a new sulfated saponin from sea cucumber, exhibits anti-angiogenic and anti-tumor activities in vitro and in vivo. Cancer Biol Ther, 4, 874-82. crossref(new window)

Tilli CM, Stavast-Koey AJ, Ramaeker FC, et al (2002). Bax expression and growth behavior of basal cell carcinomas. J Cutan Pathol, 29, 79-87. crossref(new window)

Woo M, Hakem R, Soengas MS, et al (1998). Essential contribution of caspase-3/CPP32 to apoptosis and its associated nuclear change. Genes Dev, 12, 806-19. crossref(new window)

Ye J, Coulouris G, Zaretskaya I, et al (2012). Primer-BLAST: A tool to design target-specific primers for polymerase chain reaction. BMC Bioinformatics, 13, 134. crossref(new window)

Zheng TS, Schlosser SF, Dao T, et al (1998). Caspase-3 controls both cytoplasmic and nuclear events associated with Fasmediated apoptosis in vivo. Proc Natl Acad Sci USA, 95, 13618-23. crossref(new window)