Exploring cytotoxicity of cordycepin loaded nanovesicles against (HCT116) colon cancer cells: Optimization and cellular evaluation

• Published in: Biomedicine & pharmacotherapy Vol. 154; p. 113619
• Main Authors: Alhakamy, Nabil A, Fahmy, Usama A
• Format: Journal Article
• Language: English
• Published: France Elsevier 01.10.2022
• Subjects: Apoptosis; Cancer; Cell Survival; Colonic Neoplasms - drug therapy; Colonic Neoplasms - pathology; Colorectal cancer; Cordycepin; Cytotoxicity; Deoxyadenosines - pharmacology; HCT116 Cells; Humans; Nanoparticles; Necrosis; Nanoparticles; Cytotoxicity; Cordycepin; Colorectal cancer; Cancer; Necrosis
• ISSN: 0753-3322; 1950-6007
• DOI: 10.1016/j.biopha.2022.113619

Numerous researchers have investigated cordycepin (COR) as an anti-tumor compound. COR has been documented to have cytotoxic effects on several cancer cells. The current work used a Box-Behnken mathematical design to minimize COR's size. The design incorporated COR concentration, phospholipid concentration and sonication time as variables to minimize the vesicles of COR emulsomes (COR-EMLs). To evaluate degree of improvement of COR cytotoxicity against colorectal cancer (HCT116) cells, cell viability, cell cycle analysis and apoptosis have been assessed. In addition, wound scratching and mitochondrial membrane potential were evaluated. Results of Box-Behnken design achieved COR-EMLs sizes in range from 91.54 ± 2.3-343.83 ± 3.7 nm. Moreover, the optimized formula morphology's was evaluated using transmission electron microscope and showed nanospheres in range of 100 nm. COR released from COR-EMLs exceeded 80% after 12 h.The half-maximal inhibitory concentration (IC ) of the refined COR-EML formula was about four times lower than that of COR-raw. The cell cycle study revealed that administration of COR-EML considerably hindered HCT116 cellular propagation in contrast to plain emulsomes (EMLs) and COR-raw with a denser cell compilation in G2/M. Moreover, the optimized formula notably enhanced the proportion of cells in both the initial and late phases of apoptosis. The augmentation of COR cytotoxicity was confirmed by its inhibition of cancer cell wound healing by approximately 40%. The mitochondrial membrane potential was significantly lower than in cells treated with COR-raw and EMLs. Finally, loading COR into the EMLs increased COR's capacity to lower mitochondrial membrane functionality and significantly improved its cytotoxicity.