Boldine induces cell cycle arrest and apoptosis in T24 human bladder cancer cell line via regulation of ERK, AKT, and GSK-3β

• Published in: Urologic oncology Vol. 32; no. 1; pp. 36.e1 - 36.e9
• Main Authors: Gerhardt, Daniéli, Ph.D, Bertola, Gabriela, Dietrich, Fabrícia, M.Sc, Figueiró, Fabrício, PharmD, Zanotto-Filho, Alfeu, Ph.D, Moreira Fonseca, José Cláudio, Ph.D, Morrone, Fernanda Bueno, Ph.D, Barrios, Carlos Henrique, Ph.D, Battastini, Ana Maria O., Ph.D, Salbego, Christianne G., Ph.D
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 2014
• Subjects: Antineoplastic Agents - pharmacology; Apoptosis; Aporphines - pharmacology; Bladder cancer; Boldine; Cell Cycle Checkpoints - drug effects; Cell Line, Tumor; Cell Proliferation - drug effects; Cell signaling; Cell Survival; Drug Screening Assays, Antitumor; Extracellular Signal-Regulated MAP Kinases - metabolism; G2/M-phase arrest; Glycogen Synthase Kinase 3 - metabolism; Glycogen Synthase Kinase 3 beta; Humans; Peumus - chemistry; Plant Extracts - pharmacology; Proto-Oncogene Proteins c-akt - metabolism; Rhodamines; Signal Transduction; Tetrazolium Salts; Thiazoles; Urinary Bladder Neoplasms - metabolism; Urinary Bladder Neoplasms - pathology; Urology; Bladder cancer; Boldine; Cell signaling; G 2/M-phase arrest; Apoptosis; G2/M-phase arrest; G/M-phase arrest
• ISSN: 1078-1439; 1873-2496
• DOI: 10.1016/j.urolonc.2013.02.012

Abstract Objective Bladder cancer is one of the most prevalent genitourinary malignancies. Despite active chemotherapy regimens, patients with bladder cancer suffer from a high rate of tumor recurrence. Thus, new approaches and agents to improve quality of life and survival still need to be developed. The objective of the present study was to evaluate the effect and underlying mechanisms of boldine, an aporphine alkaloid of Peumus boldus, on bladder cancer proliferation and cell death. Methods Sulforhodamine B assay, Tetrazolium reduction assay, Flow Cytometry Analysis, Ecto-5’-nucleotidase activity and Western blot assay were performed. Results The results showed that boldine was able to reduce cell viability and cell proliferation in T24 cells. In addition, boldine arrests the cell cycle at G2/M-phase and cause cell death by apoptosis. Boldine-induced inhibition of cell growth and cell cycle arrest appears to be linked to inactivation of extracellular signal–regulated kinase protein (ERK). Additionally, the efficacy of boldine in apoptosis-induced in T24 cells is correlated with modulation of AKT (inactivation) and glycogen synthase kinase-3β (GSK-3β) (activation) proteins. Conclusions The present findings may, in part, explain the therapeutic effects of boldine for treatment of urinary bladder cancer.