Cryptolepine inhibits hepatocellular carcinoma growth through inhibiting interleukin-6/STAT3 signalling
Seth A Domfeh1,2, Patrick W Narkwa3, Osbourne Quaye1,2
1West African Centre for Cell Biology of Infectious Pathogens, University of Ghana, Legon, Ghana.
Background:
Diverse signalling pathways are involved in carcinogenesis and one of such pathways implicated in many cancers is the interleukin 6/signal transducer and activator of transcription 3 (IL-6/STAT3) signalling pathway. Therefore, inhibition of this pathway is targeted as an anti-cancer intervention. This study aimed to establish the effect of cryptolepine, which is the main bioactive alkaloid in the medicinal plant Cryptolepis sanguinolenta, on the IL-6/STAT3 signalling pathway.
Methods:
First, the effect of cryptolepine on the IL-6/STAT3 pathway in human hepatoma cells (HepG2 cells) was screened using the Cignal Finder Multi-Pathway Reporter Array. Next, to confirm the effect of cryptolepine on the IL-6/STAT3 signalling pathway, the pathway was activated using 200 ng/mL IL-6 in the presence of 0.5-2 μM cryptolepine. The levels of total STAT3, p-STAT3 and IL-23 were assessed by ELISA.
Results:
Cryptolepine downregulated 12 signalling pathways including the IL-6/STAT3 signalling pathway and upregulated 17 signalling pathways. Cryptolepine, in the presence of IL-6, decreased the levels of p-STAT3 and IL-23 in a dose-dependent fashion.
Conclusion:
Our results demonstrated that cryptolepine inhibits the IL-6/STAT3 signalling pathway, and therefore cryptolepine-based remedies such as Cryptolepis sanguinolenta could potentially be used as an effective immunotherapeutic agent for hepatocellular carcinoma and other cancers.
Insights
Cryptolepine, derived from Cryptolepis sanguinolenta, inhibits the interleukin-6/signal transducer and activator of transcription 3 (IL-6/STAT3) pathway. This suggests potential for cancer immunotherapies.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- The interleukin-6/signal transducer and activator of transcription 3 (IL-6/STAT3) pathway is crucial in carcinogenesis.
- Targeting this pathway is a key anti-cancer strategy.
- Cryptolepine is a bioactive alkaloid from the medicinal plant Cryptolepis sanguinolenta.
Purpose of the Study:
- To investigate the effect of cryptolepine on the IL-6/STAT3 signalling pathway.
- To evaluate cryptolepine as a potential anti-cancer agent.
Main Methods:
- Screening of cryptolepine's effect on signalling pathways in HepG2 cells using a reporter array.
- Activation of the IL-6/STAT3 pathway with IL-6 and varying concentrations of cryptolepine.
- Quantification of total STAT3, p-STAT3, and IL-23 levels via ELISA.
Main Results:
- Cryptolepine downregulated 12 signalling pathways, including IL-6/STAT3.
- In the presence of IL-6, cryptolepine dose-dependently reduced p-STAT3 and IL-23 levels.
Conclusions:
- Cryptolepine effectively inhibits the IL-6/STAT3 signalling pathway.
- Cryptolepis sanguinolenta, containing cryptolepine, may serve as an immunotherapeutic agent for cancers like hepatocellular carcinoma.
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