Hadis Alidadi1,2, Atefeh Ashtari3,4, Azin Samimi5, Masoud Ali Karami6, Layasadat Khorsandi7,8. 1. Toxicology Research Center, Medical Basic Sciences Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran. 2. Department of Toxicology, Faculty of Pharmacy, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran. 3. Cellular and Molecular Research Center, Medical Basic Sciences Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran. 4. Department of Anatomical Sciences, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran. 5. Legal Medicine Research Center, Legal Medicine Organization, Ahvaz, Iran. 6. School of Pharmacy, Nanotechnology Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran. 7. Cellular and Molecular Research Center, Medical Basic Sciences Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran. khorsandi_cmrc@yahoo.com. 8. Department of Anatomical Sciences, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran. khorsandi_cmrc@yahoo.com.
Abstract
BACKGROUND: Among the flavonoids, Myricetin (MCN) has negligible side effects and anti-cancer properties. However, the therapeutic potential of MCN has been limited mainly by its low bioavailability. Nanocarriers improve the bioavailability and stability of flavonoids. The toxic effects of MCN loaded in solid lipid nanoparticles (MCN-SLNs) on the HT-29 human colorectal cancer cells were investigated in this study. METHODS AND RESULTS: HT-29 cells were exposed to the 30 µmol MCN or MCN-SLNs for 24 h. Colony formation, cell viability, apoptosis, and expression of the Bax, Bcl-2, and AIF (apoptosis-inducing factor) have been investigated. Mitochondrial membrane potential (MMP) and reactive oxygen species (ROS) generation were also measured. The MCN-SLNs with appropriate characteristics and a slow sustained MCN release until 48 h made. MCN-SLNs could diminish colony numbers and survival of the HT-29 cells. The apoptosis index of MCN-SLNs-treated cells significantly increased compared to the free MCN (p < 0.001). The expression of Bax and AIF were elevated (p < 0.01 and p < 0.001, respectively) while Bcl-2 expression was decreased in MCN-SLNs treatment (p < 0.05). Moreover, MCN-SLNs significantly enhanced the ROS formation and reduced MMP compared to the free MCN-treated cells (p < 0.01). CONCLUSIONS: The SLN formulation of MCN can effectively induce colon cancer cell death by raising ROS formation and activating the apoptosis process.
BACKGROUND: Among the flavonoids, Myricetin (MCN) has negligible side effects and anti-cancer properties. However, the therapeutic potential of MCN has been limited mainly by its low bioavailability. Nanocarriers improve the bioavailability and stability of flavonoids. The toxic effects of MCN loaded in solid lipid nanoparticles (MCN-SLNs) on the HT-29 human colorectal cancer cells were investigated in this study. METHODS AND RESULTS: HT-29 cells were exposed to the 30 µmol MCN or MCN-SLNs for 24 h. Colony formation, cell viability, apoptosis, and expression of the Bax, Bcl-2, and AIF (apoptosis-inducing factor) have been investigated. Mitochondrial membrane potential (MMP) and reactive oxygen species (ROS) generation were also measured. The MCN-SLNs with appropriate characteristics and a slow sustained MCN release until 48 h made. MCN-SLNs could diminish colony numbers and survival of the HT-29 cells. The apoptosis index of MCN-SLNs-treated cells significantly increased compared to the free MCN (p < 0.001). The expression of Bax and AIF were elevated (p < 0.01 and p < 0.001, respectively) while Bcl-2 expression was decreased in MCN-SLNs treatment (p < 0.05). Moreover, MCN-SLNs significantly enhanced the ROS formation and reduced MMP compared to the free MCN-treated cells (p < 0.01). CONCLUSIONS: The SLN formulation of MCN can effectively induce colon cancer cell death by raising ROS formation and activating the apoptosis process.
Authors: Allison Knickle; Wasundara Fernando; Anna L Greenshields; H P Vasantha Rupasinghe; David W Hoskin Journal: Food Chem Toxicol Date: 2018-05-06 Impact factor: 6.023