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

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

  • Urol Oncol. 2014 Jan;32(1):36.e1-9. doi: 10.1016/j.urolonc.2013.02.012.
Daniéli Gerhardt 1 Gabriela Bertola 2 Fabrícia Dietrich 2 Fabrício Figueiró 2 Alfeu Zanotto-Filho 2 José Cláudio Moreira Fonseca 2 Fernanda Bueno Morrone 3 Carlos Henrique Barrios 4 Ana Maria O Battastini 2 Christianne G Salbego 2
Affiliations

Affiliations

  • 1 Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brasil. Electronic address: danieli83@yahoo.com.br.
  • 2 Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brasil.
  • 3 Faculdade de Farmácia, Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS), Porto Alegre, RS, Brasil.
  • 4 Faculdade de Medicina, Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS), Porto Alegre, RS, Brasil.
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.

Keywords

Apoptosis; Bladder cancer; Boldine; Cell signaling; G(2)/M-phase arrest.

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