The construction of the multifunctional targeting ursolic acids liposomes and its apoptosis effects to C6 glioma stem cells

Abstract

Brain gliomas, one of the most fatal tumors to human, severely threat the health and life of human. They are capable of extremely strong invasion ability. And invasive glioma cells could rapidly penetrate into normal brain tissues and break them. We prepared a kind of functional liposomes, which could be transported acrossing the blood-brain barrier (BBB) and afterwards induce the apoptosis of glioma stem cells. In this research, we chose ursolic acids (UA) as an anti-cancer drug to inhibit the growth of C6 glioma cells, while epigallocatechin 3-gallate(EGCG) as the agent that could induce the apoptosis of C6 glioma stem cells. With the targeting ability of MAN, the liposomes could be delivered through the BBB and finally were concentrated on the brain gliomas. Cell experiments in vitro demonstrated that the functional liposomes were able to significantly enhance the anti-cancer effects of the drugs due to promoting the apoptosis and endocytosis effects of C6 glioma cells and C6 glioma stem cells at the same time. Furthermore, the evaluations through animal models showed that the drugs could obviously prolong the survival period of brain glioma-bearing mice and inhibit the tumor growth. Consequently, multifunctional targeting ursolic acids liposomes could potentially improve the therapeutic effects on C6 glioma cells and C6 glioma stem cells.

Fruit-Derived Polysaccharides and Terpenoids: Recent Update on the Gastroprotective Effects and Mechanisms

“…With regards to gastric cancer, ursolic acid have been tested in a few cell lines (AGS, BGC823, SGC7901, and SNU-484) and were shown to induce apoptosis via downregulation of Bcl-2 and Bax level, inhibition of cyclooxygenase 2, and increase in caspase-3, and -8 activities ( Liu, 1995 ; Chattopadhyay et al, 2002 ; Woźniak et al, 2015 ). Few researches have encapsulated ursolic acid in liposomes and reported an enhanced efficiency in targeting and eliminating cancer including the remnant cancer stem cells ( Wang et al, 2016 ; Ying et al, 2017 ). Pre-treatment of BGC-823 human adenocarcinoma gastric cancer cell line with ursolic acid could sensitize the cells to the toxicity of radiation ( Yang et al, 2015 ).…”

Evaluation of the In Vitro Cytotoxic Activity of Ursolic Acid PLGA Nanoparticles against Pancreatic Ductal Adenocarcinoma Cell Lines

“…One of our hypotheses is very strong interactions between UA and phospholipids, which negates the cytotoxic potential of UA. However, to this date, there are few published liposomal formulations of UA, where the triterpenoid did not lose its cytotoxicity towards cells [ 67 , 68 , 69 , 70 ]. Yet, there is no liposomal formulation of UA used in potential PDAC treatment, maybe because of this unknown phenomenon.…”

Stem cells as delivery vehicles for regenerative medicine-challenges and perspectives

“…The loading process is, however, less efficient than in the case of polymeric nanoparticles. The higher concentration of liposomes required for efficient loading may interfere with cell viability, a process that is cell dependent[ 83 ].…”