Amany A Abdin1, Nema A Soliman2, Eman M Saied3. 1. Department of Pharmacology, Faculty of Medicine, Tanta University, Tanta, Egypt. Electronic address: amanyabdin@med.tanta.edu.eg. 2. Department of Medical Biochemistry, Faculty of Medicine, Tanta University, Tanta, Egypt. 3. Department of Pathology, Faculty of Medicine, Kafr El-Sheikh University, Tanta, Egypt.
Abstract
BACKGROUND: β-Adrenergic signaling could contribute to initiation and progression of breast cancer. This research investigated some potential mechanisms of propranolol in amelioration of progression and survival in breast cancer. METHODS AND RESULTS: Solid Ehrlich Carcinoma (SEC) xenograft model was induced in 30 mice divided into 3 groups; where group I served as untreated SEC group. In groups II and III, propranolol treatment i.p. in low (5mg/kg) and high dose (10mg/kg) caused significant increase in interleukin-10 (IL-10) and decrease in heat shock protein 70 (Hsp70) and inducible nitric oxide synthase (iNOS) activity with non significant change in visfatin in tumor tissues compared to untreated SEC. In untreated SEC, tumor volume (V) exhibited significant negative correlation with IL-10 levels and toll like receptor 2 (TLR2) expression with significant positive correlation with Hsp70 levels and iNOS activity. While propranolol in either doses caused reduction of tumor volume (V), and improved percentage tumor growth inhibition (% TGI) only its high dose exhibited significant impact on survival rate. Propranolol dose-dependent effect was evident for IL-10 and Hsp70, and even only the high dose significantly increased and decreased TLR2 and survivin, respectively. This comes in favor of recommending high dose of propranolol in cancer therapy. Nonetheless, use of low dose cannot be ignored when benefit to risk balance have to be considered. CONCLUSIONS: Propranolol could provide palliative effects in progression and survival of breast cancer that are mainly mediated via direct immunomodulatory and apoptotic mechanisms and probably associated with indirect anti-angiogenic activity.
BACKGROUND: β-Adrenergic signaling could contribute to initiation and progression of breast cancer. This research investigated some potential mechanisms of propranolol in amelioration of progression and survival in breast cancer. METHODS AND RESULTS: Solid Ehrlich Carcinoma (SEC) xenograft model was induced in 30 mice divided into 3 groups; where group I served as untreated SEC group. In groups II and III, propranolol treatment i.p. in low (5mg/kg) and high dose (10mg/kg) caused significant increase in interleukin-10 (IL-10) and decrease in heat shock protein 70 (Hsp70) and inducible nitric oxide synthase (iNOS) activity with non significant change in visfatin in tumor tissues compared to untreated SEC. In untreated SEC, tumor volume (V) exhibited significant negative correlation with IL-10 levels and toll like receptor 2 (TLR2) expression with significant positive correlation with Hsp70 levels and iNOS activity. While propranolol in either doses caused reduction of tumor volume (V), and improved percentage tumor growth inhibition (% TGI) only its high dose exhibited significant impact on survival rate. Propranolol dose-dependent effect was evident for IL-10 and Hsp70, and even only the high dose significantly increased and decreased TLR2 and survivin, respectively. This comes in favor of recommending high dose of propranolol in cancer therapy. Nonetheless, use of low dose cannot be ignored when benefit to risk balance have to be considered. CONCLUSIONS:Propranolol could provide palliative effects in progression and survival of breast cancer that are mainly mediated via direct immunomodulatory and apoptotic mechanisms and probably associated with indirect anti-angiogenic activity.
Authors: Ghada A El Tawiil; Eman Ali Noaman; Mostafa A Askar; Neama Mohamed El Fatih; Hebatallah E Mohamed Journal: Integr Cancer Ther Date: 2020 Jan-Dec Impact factor: 3.279