Department of Microbiology, College of Medicine, Howard University, Washington, DC 20059, USA.
Anticancer Res. 2010 Feb;30(2):519-27.
Worldwide among men, prostate cancer ranks third in cancer occurrence and sixth in cancer mortality. A number of 1, 4-naphthoquinone derivatives have been identified that possess significant pharmacological effects associated with antitumor activities. In this study, the in vitro effects of N-(3-chloro-1,4-dioxo 1,4-dihydro-naphthalen-2-yl)-benzamide (NCDDNB) were evaluated on androgen-dependent (CWR-22) and androgen-independent (PC-3, DU-145) human prostate cancer cell lines, and on a normal bone marrow cell line (HS-5). Specifically, the in vitro activity of this compound on cell cycle regulation and apoptosis was evaluated.
Established methods of cell viability, cell cycle, Western blot and apoptosis were used.
The effect of NCDDNB on CWR-22, PC-3, DU-145 and HS-5 cells revealed significant anti-tumor activities with IC(50)s, of 2.5, 2.5, 6.5, and 25 muM respectively. The results of cell cycle analysis showed that NCDDNB arrested PC-3, DU-145, and CWR-22 cells in the G(1)-phase of the cell cycle. The compound showed no effect on the cell cycle progression in the HS-5 bone marrow cell line. These findings were further validated using Western blot analysis. NCDDNB showed the greatest amount of apoptosis in the androgen-independent PC-3 cells in a time-dependent manner with the apoptotic apex at day 5 of treatment. Furthermore, NCDDNB induced-apoptosis in DU-145 and CWR-22 cells peaked at day 3 of treatment.
Although the mechanism of action of this compound has not been completely elucidated, the effect on the cell cycle and the induction of apoptosis in different prostate cancer cell lines prompted us to carry out a more in-depth preclinical evaluation. This study suggests that NCDDNB may have an impact on treatment of prostate cancer while protecting the bone marrow.
在全球范围内，男性前列腺癌的发病率位居第三，死亡率位居第六。已经鉴定出许多 1,4-萘醌衍生物，它们具有与抗肿瘤活性相关的显著药理作用。在这项研究中，评估了 N-(3-氯-1,4-二氧代 1,4-二氢萘-2-基)-苯甲酰胺（NCDDNB）对雄激素依赖性（CWR-22）和雄激素非依赖性（PC-3、DU-145）人前列腺癌细胞系以及正常骨髓细胞系（HS-5）的体外影响。具体而言，评估了该化合物对细胞周期调控和细胞凋亡的体外活性。
使用了细胞活力、细胞周期、Western blot 和凋亡的既定方法。
NCDDNB 对 CWR-22、PC-3、DU-145 和 HS-5 细胞的作用显示出显著的抗肿瘤活性，IC50 分别为 2.5、2.5、6.5 和 25 μM。细胞周期分析结果表明，NCDDNB 将 PC-3、DU-145 和 CWR-22 细胞阻滞在细胞周期的 G1 期。该化合物对 HS-5 骨髓细胞系的细胞周期进展没有影响。这些发现使用 Western blot 分析进一步得到验证。NCDDNB 以时间依赖性方式在雄激素非依赖性 PC-3 细胞中引起最大量的细胞凋亡，在治疗第 5 天达到凋亡峰值。此外，NCDDNB 在 DU-145 和 CWR-22 细胞中诱导的细胞凋亡在治疗第 3 天达到峰值。
尽管该化合物的作用机制尚未完全阐明，但对不同前列腺癌细胞系的细胞周期的影响和诱导细胞凋亡促使我们进行更深入的临床前评估。这项研究表明，NCDDNB 可能对治疗前列腺癌同时保护骨髓产生影响。
