A Novel Imidazopyridine Derivative Exerts Anticancer Activity by Inducing Mitochondrial Pathway-Mediated Apoptosis
Juanli Wang1, Hong Wu2, Guiting Song1
1National & Local Joint Engineering Research Center of Targeted and Innovative Therapeutics, Chongqing Engineering Laboratory of Targeted and Innovative Therapeutics, Chongqing Key Laboratory of Kinase Modulators as Innovative Medicine, Chongqing Collaborative Innovation Center of Targeted and Innovative Therapeutics, College of Pharmacy & International Academy of Targeted Therapeutics and Innovation, Chongqing University of Arts and Sciences, Chongqing 402160, China.
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.
Insights
Novel imidazopyridine compound 9i shows anticancer effects by inducing apoptosis in human cervical cancer cells. This compound may lead to new cancer therapeutics.
Area of Science:
- Medicinal Chemistry
- Molecular Biology
- Cancer Research
Background:
- Cancer presents a significant therapeutic challenge due to limited effective treatments.
- Novel chemotherapeutic agents are urgently needed to combat cancer.
- Imidazopyridine derivatives represent a class of compounds with potential anticancer activity.
Purpose of the Study:
- To investigate the anticancer effects of a novel imidazopyridine compound, designated 9i.
- To elucidate the molecular mechanisms underlying the observed anticancer activity of compound 9i.
Main Methods:
- Human cervical cancer cells (HeLa) were treated with compound 9i.
- Cell viability was assessed using MTT assays and clonogenicity was evaluated via colony formation assays.
- Apoptosis, mitochondrial membrane potential, and apoptosis-related protein expression were analyzed using propidium iodide staining, fluorescence-activated cell sorting (FACS), and western blotting.
Main Results:
- Compound 9i demonstrated a time- and dose-dependent suppression of HeLa cell viability.
- Treatment with compound 9i induced mitochondrial outer membrane permeabilization (MOMP).
- The compound activated the caspase cascade, leading to apoptosis in cancer cells.
Conclusions:
- Compound 9i effectively induces apoptosis through the mitochondrial pathway in human cervical cancer cells.
- These findings suggest that compound 9i holds promise as a potential lead compound for developing new cancer therapeutics.
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