Piceatannol-Loaded Emulsomes Exhibit Enhanced Cytostatic and Apoptotic Activities in Colon Cancer Cells
Nabil A. Alhakamy, Shaimaa M. Badr-Eldin, Osama A. A. Ahmed, Hani Z. Asfour, Hibah M. Aldawsari, Mardi M. Algandaby, Basma G. Eid, Ashraf B. Abdel‐Naim, Zuhier Awan, Adel F. Alghaith, Ahmed L. Alaofi, Amir I. Mohamed, Solomon Z. Okbazghi, Mohammed W. Al-Rabia, Usama A. Fahmy
Abstract
Piceatannol (PIC), a naturally occurring polyphenolic stilbene, has pleiotropic pharmacological activities. It has reported cytotoxic activities against different cancer cells. In the present study, PIC emulsomes (PIC-E) were formulated and assessed for cytotoxic activity. A Box–Behnken design was employed to investigate the influence of formulation factors on particle size and drug entrapment. After optimization, the formulation had a spherical shape with a particle size of 125.45 ± 1.62 nm and entrapment efficiency of 93.14% ± 2.15%. Assessment of cytotoxic activities indicated that the optimized PIC-E formula exhibited significantly lower IC50 against HCT 116 cells. Analysis of the cell cycle revealed the accumulation of cells in the G2-M phase as well as increased cell fraction in the sub-G1 phase, an indication of apoptotic-enhancing activity. Staining of cells with Annexin V indicated increased early and late apoptosis. Further, the cellular contents of caspase - 3 and Bax/Bcl-2 mRNA expression were significantly elevated by PIC-E. In addition, the mitochondrial membrane potential (MMP) was disturbed and reactive oxygen species (ROS) production was increased. In conclusion, PIC-E exhibited superior cell death-inducing activities against HCT 116 cells as compared to pure PIC. This is mediated, at least partly, by enhanced pro-apoptotic activity, disruption of MMP, and stimulation of ROS generation.