Quinacrine Inhibits Cell Growth and Induces Apoptosis in Human Gastric Cancer Cell Line SGC-7901

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• 作者：Xiaoyang Wu ; PhD¹ ; ² ; Yunliang Wang ; PhD³ ; Hongwei Wang ; PhD⁴ ; Qiang Wang ; PhD⁵ ; ^{qwang@medicine.bsd.uchicago.edu} ; Lin Wang ; MS⁶ ; Jingcheng Miao ; MS⁷ ; Fengmei Cui ; PhD⁷ ; Jinzhi Wang ; PhD⁷ ; ^{zuguodadi@msn.com}
• 关键词：apoptosis ; Bax ; Bcl-2 ; p53 ; quinacrine ; SGC-7901 cells
• 刊名：Current Therapeutic Research
• 出版年：2012
• 期刊代码：75_0011393x
• 类别：med
• 出版时间：February-April, 2012
• 卷：73
• 期：1-2
• 页码：52-64
• 文件大小：1071 K

摘要

Background

Quinacrine (QC), an antimalarial drug, has been shown to possess anticancer effect both in vitro (cancer cell lines) and in vivo (mouse models). In the cancer cells, QC can simultaneously suppress nuclear factor-魏B and activate p53 signaling, which results in the induction of the apoptosis in these cells. However, the experimental results come from a few limited cancer cell lines, and the detailed mechanisms remain unknown.

Objective

This study investigated the tumor-killing effects of QC on gastric cancer cells as well as underlying molecular pathways.

Methods

SGC-7901 cells were treated with or without QC at different concentrations for 24 hours. The effect of QC on the inhibition of SGC-7901 cell proliferation was assessed by Cell Counting Kit-8 assay. Apoptosis was detected by examining nuclear morphology and quantifying phosphatidylserine externalization. Alterations in cellular morphology were analyzed by laser scanning confocal microscopy for fluorescent analysis. Cell cycle analysis was performed by propidium iodide (PI) staining and flow cytometry. The enzyme activity changes of caspase-3 were detected by colorimetry expression method. Western blot analysis was used to detect the changes in the protein level of Bax, Bc1-2, p53, and cytochrome c in cytosol of SGC-7901 cells.

Results

Our results showed that QC could significantly inhibit the growth of SGC-7901 cells in a dose-dependent manner, with the IC₅₀ mean (SD) value of 16.18 (0.64) 渭M, compared with nontreated controls. QC treatment (15 渭M) could also induce apoptosis in SGC-7901 cells (26.30%[5.31%], compared with control group of 3.37%[0.81%]; P < 0.01), and the increasing phosphatidylserine level and the accumulation of chromatin nucleation in QC-treated cells provided further evidence. In addition, cell cycle analysis with PI staining showed that a significant S enriches, increasing from 12.00%(1.24%) (control) to 20.94%(2.40%) (QC treatment) (P < 0.01). Furthermore, increased activities of caspase-3 (increasing from 0.108 [0.019] to 0.628 [0.068]; P < 0.01) were observed in SGC-7901 cells treated with 15 渭M QC. Western blot analysis showed that QC treatment significantly increased the levels of proapoptotic proteins, including cytochrome c, Bax, and p53, and decreased the levels of antiapoptotic protein Bcl-2, thus shifting the ratio of Bax/Bcl-2 in favor of apoptosis.

Conclusions

Our findings suggest that QC can significantly inhibit cell growth and induce apoptosis in SGC-7901 cells, which involves p53 upregulation and caspase-3 activation pathway.