Cardiomyocyte apoptosis vs autophagy with prolonged doxorubicin treatment: Comparison with osteosarcoma cells
MetadataShow full item record
Objective Doxorubicin (Dox) is a frontline chemotherapeutic against osteosarcoma (OS) that is plagued by side effects, particularly in the heart. The specific objective of this article is to investigate whether low-dose Dox treatment had pro-autophagic effects in cardiomyocytes as well as osteosarcoma cells. Methods This study characterises apoptotic (Bax) and autophagic (Beclin-1) biomarker levels in human OS and cardiomyocyte cell lines as well as in various tissues when mice are exposed to low (1-mg/kg, thrice weekly) and high (3-mg/kg thrice weekly) dose Dox for a month. Key findings There was a decrease in Bax and increase in Beclin-1 in cardiac tissue in the high-dose group. Dox decreased Beclin-1 in the skin and liver, with no clear indication in the stomach, small intestine and testis. At low Dox doses of 10 and 100-nm in cardiomyocytes and OS cells, there is a pro-apoptotic effect, with a quicker response in the 100-nm condition, and a slower but steady increase of a pro-apoptotic response at the lower 10-nm dose. However, electron microscopy images revealed changes to human OS cells that resembled autophagy. Human prostate, breast and colorectal cells treated with 10-nm Dox showed ~ 40% reduction in cell viability after 24-h. Conclusion In culture, cells of both cardiomyocytes and OS revealed a predominant pro-apoptotic response at the expense of autophagy, although both seemed to be occurring in vivo.
Showing items related by title, author, creator and subject.
Potent long-term cardioprotective effects of single low-dose insulin-like growth factor-1 treatment postmyocardial infarctionO'Sullivan, J.; Leblond, A.; Kelly, G.; Kumar, A.; Metharom, Pat; Büneker, C.; Alizadeh-Vikali, N.; Hristova, I.; Hynes, B.; O'Connor, R.; Caplice, N. (2011)Background-Insulin-like growth factor-1 (IGF-1) is recognized as an important regulator of cardiac structure and cardiomyocyte homeostasis. The prosurvival and antiapoptotic effects of IGF-1 have been investigated in vitro ...
Induction of apoptosis in murine malignant mesothelioma cell lines: gene expression and susceptibilityKusmiaty (2003)Malignant mesothelioma (MM) is an aggressive and highly chemo-resistant tumour of the mesothelium. Asbestos is indicated as the environmental factor most commonly associated with mesothelioma. The chemo-resistance is ...
Apoptosis induction of poly-S-nitrosated human serum albumin in resistant solid tumor under hypoxia can be restored by phosphodiesterase 5 inhibitionIkeda, M.; Ishima, Y.; Chuang, Victor; Ikeda, T.; Kinoshita, R.; Watanabe, H.; Ishida, T.; Otagiri, M.; Maruyama, T. (2016)© 2017.Poly-S-nitrosated human serum albumin (Poly-SNO-HSA) delivered and accumulated nitric oxide (NO) in tumors and induces apoptosis. Tumor hypoxia is strongly associated with malignant progression and tumor resistance ...