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. 2020 Aug 25:2020:4929053.
doi: 10.1155/2020/4929053. eCollection 2020.

A Novel Imidazopyridine Derivative Exerts Anticancer Activity by Inducing Mitochondrial Pathway-Mediated Apoptosis

Juanli Wang  1 , Hong Wu  2 , Guiting Song  1 , Donglin Yang  1 , Jiuhong Huang  1 , Xiaofang Yao  1 , Hongxia Qin  1 , ZhongZhu Chen  1 , Zhigang Xu  1 , Chuan Xu  2
Affiliations

A Novel Imidazopyridine Derivative Exerts Anticancer Activity by Inducing Mitochondrial Pathway-Mediated Apoptosis

Juanli Wang et al. Biomed Res Int. .

Abstract

Background: Cancer remains a major clinical challenge because of the lack of effective drug for its treatment. To find out novel cancer chemotherapeutic molecules, we explored the anticancer effect of novel imidazopyridine compound 9i and also investigated the underlying molecular mechanism.

Methods: Human cervical cancer cell (HeLa) viability was measured by an MTT assay after treatment with compound 9i. Clonogenicity of HeLa cells was investigated by an in vitro colony formation assay. Cell death was visualized by propidium iodide (PI) staining. Fluorescence-activated cell sorting (FACS) was used to determine apoptosis and mitochondrial membrane potential in HeLa cells. The expression level of apoptosis-related proteins was also determined by western blot.

Results: Compound 9i suppressed HeLa cell viability in a time- and dose-dependent manner. Compound 9i induced mitochondrial outer membrane permeabilization (MOMP), activated caspase cascade, and finally resulted in apoptosis.

Conclusion: Compound 9i induces mitochondrial pathway-mediated apoptosis in human cervical cancer cells, suggesting that 9i could be a potential lead compound to be developed as a cancer therapeutic molecule.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Compound 9i inhibits HeLa cell survival in a time- and concentration-dependent manner. (a) Scheme of compound 9i. (b) Hela cell viability after different concentrations of compound 9i treated for 48 hours. (c) HeLa cell survival rate after indicated concentrations of compound 9i treatment for 24, 48, and 72 hours, respectively. Cell viability was measured using the MTT assay. Survival rate equals to compound 9i-treated cells compared to vehicle control cells; DMSO was used as a vehicle control. Data is represented as mean ± SD (n = 3). Significance was tested by Student's t-test (∗p < 0.05, ∗∗p < 0.01).
Figure 2
Figure 2
Compound 9i inhibits colony growth. (a-d) Crystal violet staining of the HeLa cell colony after various dosages of compound 9i (0, 5, 10, and 20 μM) treatment. DMSO was used as a vehicle control.
Figure 3
Figure 3
Compound 9i induces cell death. Fluorescence images of (a, d) DAPI- and (b, e) PI-stained cells. HeLa cells were treated with (a–c) a vehicle control or (d–f) 5 μM of 9i for 24 hours and stained with DAPI and PI. Arrowheads indicate the cells with condensed chromatin and PI staining. DMSO was used as a vehicle control. DAPI was used to stain the nucleus. Scale bar represents 100 μm.
Figure 4
Figure 4
Compound 9i induces apoptosis in human cervical cancer cells. (a) Representative scatter plots showing the distribution of annexin V and PI staining for control- and compound 9i-treated HeLa cells. DMSO was used as a vehicle control. (b) Quantitative analysis of the percentage of apoptotic cells by FACS analysis. Values are represented as the mean ± SD (n = 3). Significance was tested by Student's t-test (∗p < 0.05, ∗∗p < 0.01 versus DMSO-treated cells). (c) Western blot was used to determine the protein level of caspase in DMSO- or compound 9i-treated HeLa cells. The intensity of the bands was measured, and the fold change of the intensity was compared with that of the control and indicated below the bands. The expression of cleaved caspase-9 was statistically analyzed in Figure S2a. Tubulin was used as a loading control. The results were representative of three independent experiments.
Figure 5
Figure 5
Compound 9i induces mitochondria-dependent apoptosis in human cervical cancer cells. (a) Representative scatter plots showing the distribution of rhodamine 123 and PI staining for control- and compound 9i-treated HeLa cells. DMSO was used as a vehicle control. (b) Quantitative analysis of the percentage of cells with high ∆Ψm by FACS analysis. Values are represented as the mean ± SD (n = 3). Significance was tested by Student's t-test (∗∗p < 0.01, ∗∗∗p < 0.01 versus DMSO-treated cells). (c) Western blot was used to determine the expression level of apoptosis-related proteins in DMSO- or compound 9i-treated HeLa cells. The intensity of the bands was measured, and the fold change of the intensity was compared with that of the control and indicated below the bands. The expression of Bcl-xL was statistically analyzed in Figure S2b. Tubulin was used as a loading control. The results were representative of three independent experiments.
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