Doxorubicin and liposomal doxorubicin induce senescence by enhancing nuclear factor kappa B and mitochondrial membrane potential

• Published in: Life sciences (1973) 2019-09, Vol.232, p.116677-116677, Article 116677
• Main Authors: Fallah, Marjan, Mohammadi, Hamidreza, Shaki, Fatemeh, Hosseini-Khah, Zahra, Moloudizargari, Milad, Dashti, Ayat, Ziar, Ali, Mohammadpour, Abbas, Mirshafa, Atefeh, Modanloo, Mona, Shokrzadeh, Mohammad
• Format: Article
• Language: English
• Subjects: Aging; Doxorubicin; Formulations; Historical account; Inflammation; Markers; Membrane potential; Mitochondria; Mitochondrial dysfunction; Oxidative stress; P53; p53 Protein; Senescence; Senescent-associated β-galactosidase; TNF-α; Toxicity
• ISSN: 0024-3205; 1879-0631
• DOI: 10.1016/j.lfs.2019.116677

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. 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. 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.