Anticancer Potential of a Synthetic Quinoline, 9IV-c, by Inducing Apoptosis in A549 Cell and <i>In vivo</i> BALB/c Mice Models

Author(s):

Salimeh Mirzaei, Farhad Eisvand, Mojgan Nejabat, Razieh Ghodsi and Farzin Hadizadeh*   Pages 185 - 192 ( 8 )

Abstract:

<p>Background: In a previous work from the author of this study, the compound of 9IV-c, ((E)-2-(3,4- dimethoxystyryl)-6,7,8-trimethoxy-N-(3,4,5-trimethoxyphenyl)quinoline-4-amine) was synthesized, and the effects of potent activity on the multiple human tumor cell lines were evaluated considering the spindle formation together with the microtubule network. <p> Methods: Accordingly, cytotoxic activity, apoptotic effects, and the therapeutic efficiency of compound 9IV-c on A549 and C26 cell lines were investigated in this study. <p> Results: The compound 9IV-c demonstrated high cytotoxicity against A549 and C26 cell lines with IC₅₀ = 1.66 and 1.21 μM, respectively. The flow cytometric analysis of the A549 cancer cell line treated with compound 9IVc showed that This compound induced cell cycle arrest at the G2/M phase and apoptosis. Western blotting analysis displayed that compound 9IV-c also elevated the Bax/Bcl-2 ratio and increased the activation of caspase-9 and -3 but not caspase-8. <p> Conclusion: These data presented that the intrinsic pathway was responsible for 9IV-c -induced cell apoptosis. <i>In vivo</i> studies demonstrated that treatment with the compound of 9IV-c at 10 mg/kg dose led to a decrease in tumor growth compared to the control group. It was found that there was not any apparent body weight loss in the period of treatment. Also, in the vital organs of the BALB/c mice, observable pathologic changes were not detected.</p>

Keywords:

Quinoline derivative, 9IV-c, Apoptosis, In vivo antitumor activity, A549 and C26 cell lines, Bax/Bcl-2 ratio.

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