Anticancer Effects of Cinnamaldehyde Through Inhibition of ErbB2/HSF1/LDHA Pathway in 5637 Cell Line of Bladder Cancer
Zeynab Aminzadeh, Nasrin Ziamajidi, Roghayeh Abbasalipourkabir
Abstract
BACKGROUND AND OBJECTIVE: The growing prevalence of bladder cancer worldwide has become a major concern for researchers, and the side effects of chemotherapy drugs have always been a major problem in cancer treatment. Cinnamaldehyde, the active ingredient in the Cinnamon plant, has long been considered with anti-oxidant and anti-inflammatory effects. METHODS: Bladder cancer 5637 cell lines were treated with the different concentrations of Cinnamaldehyde. MTT assay was performed to evaluate cell viability at 24, 48, and 72 hours. The concentration of 0.02, 0.04, and 0.08 mg/ml of Cinnamaldehyde was selected. Apoptosis was assessed with Annexin V-FITC/PI and Hochest33258 staining. Cell migration was performed by the scratch test. To evaluate Cinnamaldehyde effect on glycolysis, the gene expression of epidermal growth factor receptor 2 (ErbB2), Heat Shock Protein Transcription Factor-1 (HSF1) and lactate dehydrogenase A (LDHA), as well as the protein levels of HSF1 and LDHA, LDH activity and finally glucose consumption and lactate production, were measured. RESULTS: Cinnamaldehyde significantly increased apoptosis rate in the 5637 cells (p<0.05). Furthermore, it significantly reduced the gene expression of ErbB2, HSF1, and LDHA, protein level of HSF1 and LDHA, LDH activity, as well as cell migration, glucose consumption, and lactate production (p<0.05). These changes were dose-dependent. CONCLUSION: Thus, Cinnamaldehyde induced apoptosis and decreased growth in 5637 cells by reducing ErbB2-HSF1- LDHA pathway.