Cinnamomum cassia Suppresses Caspase-9 through Stimulation of AKT1 in MCF-7 Cells but Not in MDA-MB-231 Cells

• Published in: PloS one 2015-12, Vol.10 (12), p.e0145216-e0145216
• Main Authors: Rad, Sima Kianpour, Kanthimathi, M S, Abd Malek, Sri Nurestri, Lee, Guan Serm, Looi, Chung Yeng, Wong, Won Fen
• Format: Article
• Language: English
• Subjects: Activation; AKT1 protein; Antioxidants; Antioxidants - metabolism; Apoptosis; Apoptosis - drug effects; Bark; Biotechnology; Breast cancer; Cancer; Care and treatment; Caspase; Caspase-8; Caspase-9; Caspases; Cell cycle; Cell Line, Tumor; Cell Proliferation - drug effects; Cervical cancer; Chemistry; Chinese cinnamon; Cinnamaldehyde; Cinnamomum aromaticum - chemistry; Cinnamomum cassia; Coumarin; Cytotoxicity; Enzymes; Gene expression; Health aspects; Herbal medicine; Humans; MCF-7 Cells; Medicinal plants; Medicine; Models, Molecular; Oxidative stress; Oxidative Stress - drug effects; Pharmaceutical sciences; Phosphorylation; Plant Extracts - pharmacology; Proteins; Proto-Oncogene Proteins c-akt - metabolism; Signal transduction; Toxicology; Tumor cell lines; Up-Regulation
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0145216

Cinnamomum cassia bark is a popular culinary spice used for flavoring and in traditional medicine. C. cassia extract (CE) induces apoptosis in many cell lines. In the present study, particular differences in the mechanism of the anti-proliferative property of C. cassia on two breast cancer cell lines, MCF-7 and MDA-MB-231, were elucidated. The hexane extract of C. cassia demonstrated high anti-proliferative activity against MCF-7 and MDA-MB-231 cells (IC50, 34 ± 3.52 and 32.42 ± 0.37 μg/ml, respectively). Oxidative stress due to disruption of antioxidant enzyme (SOD, GPx and CAT) activity is suggested as the probable cause for apoptosis initiation. Though the main apoptosis pathway in both cell lines was found to be through caspase-8 activation, caspase-9 was also activated in MDA-MB-231 cells but suppressed in MCF-7 cells. Gene expression studies revealed that AKT1, the caspase-9 suppressor, was up-regulated in MCF-7 cells while down-regulated in MDA-MB-231 cells. Although, AKT1 protein expression in both cell lines was down-regulated, a steady increase in MCF-7 cells was observed after a sharp decrease of suppression of AKT1. Trans-cinnamaldehyde and coumarin were isolated and identified and found to be mainly responsible for the observed anti-proliferative activity of CE (Cinnamomum cassia). Activation of caspase-8 is reported for the first time to be involved as the main apoptosis pathway in breast cancer cell lines upon treatment with C. cassia. The double effects of C. cassia on AKT1 gene expression in MCF-7 cells is reported for the first time in this study.