Abstract
BackgroundDiverse 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.MethodsFirst, 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.ResultsCryptolepine 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.ConclusionOur 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.
Highlights
Interleukin 6 (IL-6) is produced by several cells such as tumour cells, adipocytes, fibroblasts, macrophages, hepatocytes and endothelial cells [1, 2]
Cryptolepine and niclosamide inhibit the growth of HepG2 cells Cryptolepine inhibited the growth of HepG2 cells in a dose- and time-dependent fashion (Fig. 1A)
There was a decrease in pSTAT3 and IL-23 levels in the presence of 200 ng/mL IL-6 and 5–10 μM niclosamide (Fig. 3C and D)
Summary
Interleukin 6 (IL-6) is produced by several cells such as tumour cells, adipocytes, fibroblasts, macrophages, hepatocytes and endothelial cells [1, 2] This pleiotropic cytokine interacts with its receptor (IL-6R) to form the IL-6/IL-6R complex. Strategies are being developed to inhibit the STAT3 signalling pathway by targeting the activation of cytokine and growth factor receptors with monoclonal antibodies or receptor antagonists. 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. 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
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
