Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brasil.
Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brasil.
Urol Oncol. 2014 Jan;32(1):36.e1-9. doi: 10.1016/j.urolonc.2013.02.012. Epub 2013 Nov 13.
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.
Sulforhodamine B assay, Tetrazolium reduction assay, Flow Cytometry Analysis, Ecto-5'-nucleotidase activity and Western blot assay were performed.
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.
The present findings may, in part, explain the therapeutic effects of boldine for treatment of urinary bladder cancer.
膀胱癌是最常见的泌尿生殖系统恶性肿瘤之一。尽管采用了积极的化疗方案，膀胱癌患者仍面临着高复发率。因此，仍需要开发新的方法和药物来提高生活质量和生存率。本研究的目的是评估波多叶碱（Peumus boldus 的一种阿朴啡生物碱）对膀胱癌增殖和细胞死亡的影响及其潜在机制。
采用磺酰罗丹明 B assay、四唑氮还原 assay、流式细胞术分析、外切 5'-核苷酸酶活性和 Western blot assay 进行检测。
结果表明，波多叶碱能够降低 T24 细胞的活力和增殖能力。此外，波多叶碱可将细胞周期阻滞在 G2/M 期，并通过细胞凋亡导致细胞死亡。波多叶碱诱导的细胞生长抑制和细胞周期阻滞似乎与细胞外信号调节激酶蛋白（ERK）失活有关。此外，波多叶碱在 T24 细胞中诱导凋亡的功效与 AKT（失活）和糖原合酶激酶-3β（GSK-3β）（激活）蛋白的调节相关。
本研究结果部分解释了波多叶碱治疗膀胱癌的治疗效果。
