The anticancer activities of stichoposide D isolated from the sea cucumber Stichopus chloronotus on NTERA-2 cancer stem cells




Apoptosis, cancer stem cells, sea cucumber, Stichopus chloronotus, Stichoposide D


As reported, cancer stem cells (CSCs) are in charge of dangerous characteristics including drug resistance, metastasis, recurrence and therapeutic effectiveness. Therefore, CSCs are an important target for discovering of novel effective and specific anticancer drugs. In Vietnam, the Stichopus chloronotus sea cucumber is found as a potential biological source with various active ingredients. Particularly, the active triterpene saponin stichoposide D, which was isolated from S. chloronotus, showed strong cytotoxic activity in leukemias. Herein, stichoposide D was further studied its potential anti-CSCs activities on pluripotent human embryonic carcinomas NTERA-2 cells. The compound exhibited its promising and specific cytotoxic activities in NTERA-2 cells with the IC50 = 0.26 ± 0.02 µM, in comparison with that ranging from 0.35 ± 0.02 µM to 0.53 ± 0.03 µM (P<0.05), tested on non-CSCs cancer cell lines, which were breast carcinoma (MCF-7) and lung adenocarcinoma (SK-LU-1), respectively. The working fashion of the compound on NTERA-2 cells could be apoptotic induction. Significantly, treatment of stichoposide D at 1 µM induced 76.4% of apoptotic cells as well as 1.72 relatively fold change of caspase-3 activation in comparision with the control (P<0.05). Meanwhile, stichoposide D was the first time recorgnized its positive efficacy on reducing the number of highly expressed CD44+/CD24+ cells, which were reported as typically CSCs characterized population. The compound also exhibited some effects on NTERA-2 cell cycle of which it arrested cells at sub-G1 phase (15.03%) and prevented those CSCs to enter the S-phase for DNA synthesis. In conclusion, stichoposide D presents potential anti-CSCs activities and should be further studied for future applications.


Download data is not yet available.


Al Marzouqi N, Iratni R, Nemmar A, Arafat K, Al Sultan MA, Yasin J, Collin P, Mester J, Adrian TE, Attoub S (2011) Frondoside A inhibits human breast cancer cell survival, migration, invasion and the growth of breast tumor xenografts. European journal of pharmacology 668(1-2):25-34.

Bao B, Ahmad A, Azmi AS, Ali S, Sarkar FH (2013) Overview of cancer stem cells (CSCs) and mechanisms of their regulation: implications for cancer therapy. Curr Protoc Pharmacol Chapter 14:Unit-14.25.

Cuong NX, Vien le T, Hanh TT, Thao NP, Thao do T, Thanh NV, Nam NH, Thung do C, Kiem PV, Minh CV (2015) Cytotoxic triterpene saponins from Cercodemas anceps. Bioorganic & medicinal chemistry letters 25(16):3151-6.

Chen K, Huang YH, Chen JL (2013) Understanding and targeting cancer stem cells: therapeutic implications and challenges. Acta Pharmacol Sin 34(6):732-40.

J Prud’homme G (2012) Cancer stem cells and novel targets for antitumor strategies. Current pharmaceutical design 18(19):2838-49.

Jaggupilli A, Elkord E (2012) Significance of CD44 and CD24 as cancer stem cell markers: an enduring ambiguity. Clinical & developmental immunology 2012:708036.

Kalinovsky A, Maltsev I, Antonov A, Stonik V (1984) 13C NMR studies on the chemical structure of holothurian glycosides. Bioorg Khim 10(12):1655-63.

Minh CV, Cường NX, Đăng NH, Thảo NP, Quang TH, Tùng NH, Nam NH, Hùng NV, Kiệm PV (2012) Điểm lại các nghiên cứu hóa học và hoạt tính sinh học một số loài sinh vật biển Việt Nam trong giai đoạn 2006-2012. Vietnam Journal of Science and Technology 50(6):825.

Nam NH, Ngoc NT, Hanh TTH, Thao NP, Van Thanh N, Cuong NX, Do TT, Huong TT, Thung DC, Van Kiem P (2015) Cytotoxic biscembranoids from the soft coral Sarcophyton pauciplicatum. Chemical and Pharmaceutical Bulletin 63(8):636-40.

Ngoan BT, Hanh TTH, Vien LT, Diep CN, Thao NP, Thao DT, Thanh NV, Cuong NX, Nam NH, Thung DC (2015) Asterosaponins and glycosylated polyhydroxysteroids from the starfish Culcita novaeguineae and their cytotoxic activities. Journal of Asian natural products research 17(10):1010-7.

Ngoc NT, Huong PTM, Van Thanh N, Chi NTP, Dang NH, Cuong NX, Nam NH, Thung DC, Van Kiem P, Van Minh C (2017) Cytotoxic steroids from the Vietnamese soft coral Sinularia conferta. Chemical and Pharmaceutical Bulletin:c16-00881.

Ricardo S, Vieira AF, Gerhard R, Leitão D, Pinto R, Cameselle-Teijeiro JF, Milanezi F, Schmitt F, Paredes J (2011) Breast cancer stem cell markers CD44, CD24 and ALDH1: expression distribution within intrinsic molecular subtype. Journal of clinical pathology 64(11):937-46.

Skehan P, Storeng R, Scudiero D, Monks A, McMahon J, Vistica D, Warren JT, Bokesch H, Kenney S, Boyd MR (1990) New colorimetric cytotoxicity assay for anticancer-drug screening. JNCI: Journal of the National Cancer Institute 82(13):1107-12.

Thao NP, Cuong NX, Luyen BTT, Nam NH, Van Cuong P, Van Thanh N, Nhiem NX, Hanh TTH, Kim E-J, Kang H-K (2013) Steroidal constituents from the starfish Astropecten polyacanthus and their anticancer effects. Chemical and Pharmaceutical Bulletin 61(10):1044-51.

Thao NP, Luyen BTT, Vien LT, Tai BH, Dat LD, Cuong NX, Nam NH, Van Kiem P, Van Minh C, Kim YH (2014) Triterpene saponins from the sea cucumber Stichopus chloronotus. Natural product communications 9(5):1934578X1400900505.

Vinogradov S, Wei X (2012) Cancer stem cells and drug resistance: the potential of nanomedicine. Nanomedicine 7(4):597-615.

Yun S-H, Park E-S, Shin S-W, Ju M-H, Han J-Y, Jeong J-S, Kim S-H, Stonik VA, Kwak J-Y, Park J-I (2015) By activating Fas/ceramide synthase 6/p38 kinase in lipid rafts, stichoposide D inhibits growth of leukemia xenografts. Oncotarget 6(29):27596.




How to Cite

Cuc, N. T., Thi Nga, N., Ha Phuong, T., Thi Phuong, D., Xuan Cuong, N., Thi Mai Huong, P., Van Minh, C., & Thi Thao, D. (2020). The anticancer activities of stichoposide D isolated from the sea cucumber Stichopus chloronotus on NTERA-2 cancer stem cells. Vietnam Journal of Biotechnology, 18(2), 273–281.