Luping Zhang1, Ruitao Dong2, Yu Wang1, Longxiang Wang2, Tian Zhou3, Dongxu Jia2,3, Zhaoli Meng3. 1. The Gastroenterology & Endoscopy Center, First Hospital, Jilin University, Changchun, Jilin, China. 2. School of Life Sciences, Jilin University, Changchun, China. 3. Department of Translational Medicine Research Institute, First Hospital, Jilin University, Changchun, Jilin, China.
Abstract
CONTEXT: Physcion (Phy) exerts several pharmacological effects including anti-inflammatory, antioxidant, and antitumor properties. OBJECTIVE: This study investigates the cytotoxicity and its underlying mechanisms of Phy on breast cancer. MATERIALS AND METHODS: Human breast cancer cell MCF-7 was treated with 5-400 µM Phy for 24 h, MCF-7-xenografted BALB/c nude mice and immunosuppressive mice model induced by cyclophosphamide were intraperitoneally injected with 0.1 mL/mouse normal saline (control group) and 30 mg/kg Phy every other day for 14 or 28 days, and pathological examination, ELISA and western blot were employed to investigate the Phy anti-breast cancer property in vitro and in vivo. RESULTS: In MCF-7 cells, Phy 24 h treatment significantly reduced the cell viability at dose of 50-400 µM and 24 h, with an IC50 of 203.1 µM, and 200 µM Phy induced 56.9, 46.9, 36.9, and 46.9% increment on LDH and caspase-3, -8 and -9. In MCF-7-xenograft tumour nude mice and immunosuppressive mice, 30 mg/kg Phy treatment inhibited tumour growth from the 8th day, and reduced Bcl-2 and Bcl-xL >50%, HO-1 and SOD-1 > 70% in tumour tissues of immunosuppressive mice. In addition, Phy reduced nuclear factor erythroid 2-related factor 2 > 30% and its downstream proteins, and enhanced the phosphorylation of nuclear factor-kappa B > 110% and inhibitor of NF-кB α > 80% in the tumour tissues of BALB/c mice. DISCUSSION AND CONCLUSIONS: This research demonstrated that Phy has an anti-breast cancer property via the modulation of oxidative stress-mediated mitochondrial apoptosis and immune response, which provides a scientific basis for further research on its clinical applications.
CONTEXT: Physcion (Phy) exerts several pharmacological effects including anti-inflammatory, antioxidant, and antitumor properties. OBJECTIVE: This study investigates the cytotoxicity and its underlying mechanisms of Phy on breast cancer. MATERIALS AND METHODS: Human breast cancer cell MCF-7 was treated with 5-400 µM Phy for 24 h, MCF-7-xenografted BALB/c nude mice and immunosuppressive mice model induced by cyclophosphamide were intraperitoneally injected with 0.1 mL/mouse normal saline (control group) and 30 mg/kg Phy every other day for 14 or 28 days, and pathological examination, ELISA and western blot were employed to investigate the Phy anti-breast cancer property in vitro and in vivo. RESULTS: In MCF-7 cells, Phy 24 h treatment significantly reduced the cell viability at dose of 50-400 µM and 24 h, with an IC50 of 203.1 µM, and 200 µM Phy induced 56.9, 46.9, 36.9, and 46.9% increment on LDH and caspase-3, -8 and -9. In MCF-7-xenograft tumour nude mice and immunosuppressive mice, 30 mg/kg Phy treatment inhibited tumour growth from the 8th day, and reduced Bcl-2 and Bcl-xL >50%, HO-1 and SOD-1 > 70% in tumour tissues of immunosuppressive mice. In addition, Phy reduced nuclear factor erythroid 2-related factor 2 > 30% and its downstream proteins, and enhanced the phosphorylation of nuclear factor-kappa B > 110% and inhibitor of NF-кB α > 80% in the tumour tissues of BALB/c mice. DISCUSSION AND CONCLUSIONS: This research demonstrated that Phy has an anti-breast cancer property via the modulation of oxidative stress-mediated mitochondrial apoptosis and immune response, which provides a scientific basis for further research on its clinical applications.
Entities:
Keywords:
Breast cancer; cytotoxicity; nuclear factor erythroid 2-related factor 2; nuclear factor-kappa B
Authors: Alexander V Ivanov; Olga A Smirnova; Olga N Ivanova; Olga V Masalova; Sergey N Kochetkov; Maria G Isaguliants Journal: PLoS One Date: 2011-09-13 Impact factor: 3.240
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