Piceatannol-Loaded Emulsomes Exhibit Enhanced Cytostatic and Apoptotic Activities in Colon Cancer Cells

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.

RETRACTED: Thymoquinone-Loaded Soy-Phospholipid-Based Phytosomes Exhibit Anticancer Potential against Human Lung Cancer Cells

“…In the present study, TQ-phytosomes significantly enhanced caspase-3 content. This is in harmony with the previous reports indicating the ability of TQ to enhance cellular caspase-3 [ 34 , 38 , 39 ]. In addition, the enhanced effects of phytosomes on cleaved caspase-3 content in A543 cells has been previously demonstrated [ 39 ].…”

“…Free-TQ had been taken by passive transport, while phytosomes had been taken by endocytosis. In addition, phytosomes containing abundant phospholipids could carry amphiphilic agents to cross the cell membrane resulting in high intracellular drug concentrations [ 36 , 37 , 38 ]. However, the optimized formula showed relatively-weak cytotoxic activity against EA.hy926 non-cancerous endothelial cells.…”

The Encapsulation of Febuxostat into Emulsomes Strongly Enhances the Cytotoxic Potential of the Drug on HCT 116 Colon Cancer Cells

“…Taking into consideration the frequently reported adverse events related to the use of this drug [ 46 ], the development of new formulations able to boost its therapeutic effect, reducing the effective dose of FBX could be of great relevance for future translational studies in cancer patients. Additionally, it is also worth noting that, as showed very recently by us, drugs encapsulated into emulsomes have relatively week cytotoxic activity against non-cancerous cells compared to HCT 29 and HCT 116 colon cancer cells (five to six times higher) [ 47 ], hence having two possible therapeutic implications represented by the enhanced cytotoxicity towards cancer cells and the reduction of unwanted side effects in healthy non-cancerous cells.…”

Piceatannol Attenuates Testosterone-Induced Benign Prostatic Hyperplasia in Rats by Modulation of Nrf2/HO-1/NFκB Axis

“…However, PIC suffers relatively lower bioavailability when compared resveratrol ( Setoguchi et al, 2014 ) and other stilbenes ( Roupe et al, 2006 ). Therefore, nanoformulations have been utilized to improve pharmacokinetic and consequently pharmacodynamics characteristics of PIC ( Tambuwala et al, 2019 ; Alhakamy et al, 2020 ; Aljabali et al, 2020 ). PIC offers beneficial effects in various conditions such as: hyperlipidemia, atherosclerosis, cardiovascular diseases and cancer ( Kershaw and Kim, 2017 ).…”

“…PIC offers beneficial effects in various conditions such as: hyperlipidemia, atherosclerosis, cardiovascular diseases and cancer ( Kershaw and Kim, 2017 ). Its anti-proliferative and anti-invasive activities have been described ( Kita et al, 2012 ; Alhakamy et al, 2020 ). It has been shown in the literature that PIC had strong free radical scavenging activity that was much higher than resveratrol ( Murias et al, 2005 ).…”