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

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.

Induction of apoptosis by Stichopus chloronotus and Holothuria nobilis fractions in the human cervical cancer cell line, HeLa

Cancer is an uncontrolled growth of rapidly dividing cells. Decreased efficacy of current anticancer drugs urges to further screening and investigation for a better alternative to current chemotherapeutics. Natural products of marine origin are great sources of potential new drugs of enhanced biological activities. Thus, the work aims to investigate the cytotoxic effects along with the mode of cell death exerted by SC-8, SC-9, HN-3, HN-4 and HN-5 fractions prepared from Stichopus chloronotus and Holothuria nobilis marine-sponge on the human cervical cell line, HeLa. The fractions produced effective cytotoxicity with IC50 values at 72hr of less than 30 μg/ml in the order of HN-3 > HN-4 > SC-9 > SC-8 > HN-5. These fraction induced cytotoxicity via mediating apoptosis in HeLa cells. The early apoptosis was done by fractions via exposure of protein phosphatidylserine (PS) to the outer leaflet of the plasma membrane and late apoptosis confirmed due to the presence of fragmented DNA in treated cells. The presence of potentially bioactive compounds in these fractions might be responsible for inducing apoptosis and, thus, own potential to be a successful candidate for exploring forthcoming chemotherapeutic drugs