Marjan Fallah1, Hamidreza Mohammadi1, Fatemeh Shaki1, Zahra Hosseini-Khah2, Milad Moloudizargari3, Ayat Dashti1, Ali Ziar1, Abbas Mohammadpour4, Atefeh Mirshafa1, Mona Modanloo5, Mohammad Shokrzadeh6. 1. Department of Toxicology and Pharmacology, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran. 2. Molecular and Cell Biology Research Center, Mazandaran University of Medical Sciences, Sari, Iran. 3. Department of Immunology, School of Medicine, Student Research Committee, Shahid Beheshti University of Medical Sciences, Tehran, Iran. 4. Cell and Molecular Biology, Pharmaceutical Sciences Research Center, Mazandaran University of Medical Sciences, Sari, Iran. 5. Pharmaceutical sciences, Mazandaran University of Medical Sciences, Sari, Iran. 6. Department of Toxicology and Pharmacology, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran. Electronic address: Mslamuki@gmail.com.
Abstract
AIMS: Senescence is a state ensuing aging to eliminate age-associated damage with an irreversible cell-cycle arrest mechanism, which is historically believed to be one of the tumor responses to therapy. Doxorubicin as an anti-cancer drug has been used in cancer treatment for a long time. Liposomal doxorubicin (Ldox) is a liposomal formulation of doxorubicin, which increases the doxorubicin permanency. The aim of this study was to examine the toxicity of these two formulations by comparing them in terms of their ability to induce cellular senescence. MAIN METHODS: The study groups included a control group, three DOX (0.75, 0.5, 0.1 mg/kg/BW) and three Ldox groups (0.1, 0.05, 0.025 mg/kg/BW). Heart tissues were studied regarding oxidative stress assessment, mitochondrial function, inflammatory markers and biochemical and histopathological evaluation. Real-Time PCR was used for P53 and SA β-gal expression. KEY FINDINGS: Based on the results, the highest doses of Dox and Ldox (0.75 and 0.1 mg/kg/BW respectively) significantly increased the level of inflammatory markers and according to other factors especially p53 and SA β-gal expression, both were able to induce senescence but the changes in Ldox were less tangible than the Dox.
AIMS: Senescence is a state ensuing aging to eliminate age-associated damage with an irreversible cell-cycle arrest mechanism, which is historically believed to be one of the tumor responses to therapy. Doxorubicin as an anti-cancer drug has been used in cancer treatment for a long time. Liposomal doxorubicin (Ldox) is a liposomal formulation of doxorubicin, which increases the doxorubicin permanency. The aim of this study was to examine the toxicity of these two formulations by comparing them in terms of their ability to induce cellular senescence. MAIN METHODS: The study groups included a control group, three DOX (0.75, 0.5, 0.1 mg/kg/BW) and three Ldox groups (0.1, 0.05, 0.025 mg/kg/BW). Heart tissues were studied regarding oxidative stress assessment, mitochondrial function, inflammatory markers and biochemical and histopathological evaluation. Real-Time PCR was used for P53 and SA β-gal expression. KEY FINDINGS: Based on the results, the highest doses of Dox and Ldox (0.75 and 0.1 mg/kg/BW respectively) significantly increased the level of inflammatory markers and according to other factors especially p53 and SA β-gal expression, both were able to induce senescence but the changes in Ldox were less tangible than the Dox.
Authors: Ibrahim Y Abdelgawad; Karim T Sadak; Diana W Lone; Mohamed S Dabour; Laura J Niedernhofer; Beshay N Zordoky Journal: Pharmacol Ther Date: 2020-12-01 Impact factor: 12.310
Authors: Cielo Mae D Marquez; Jerremiah G Garcia; Jessica G Antonio; Sonia D Jacinto; Michael C Velarde Journal: Asian Pac J Cancer Prev Date: 2020-08-01