Cryptolepine inhibits hepatocellular carcinoma growth through inhibiting interleukin-6/STAT3 signalling

  • BMC Complement Med Ther. 2021 Jun 2;21(1):161. doi: 10.1186/s12906-021-03326-x.
Seth A Domfeh  1  2 ,  Patrick W Narkwa  3 ,  Osbourne Quaye  1  2 ,  Kwadwo A Kusi  1  2  4 ,  Gordon A Awandare  1  2 ,  Charles Ansah  5 ,  Alimatu Salam  6 ,  Mohamed Mutocheluh  7
Affiliations
  • 1. West African Centre for Cell Biology of Infectious Pathogens, University of Ghana, Legon, Ghana.
  • 2. Department of Biochemistry, Cell and Molecular Biology, School of Biological Sciences, University of Ghana, Legon, Ghana.
  • 3. Department of Clinical Microbiology, School of Medicine and Dentistry, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana.
  • 4. Department of Immunology, Noguchi Memorial Institute for Medical Research, College of Health Sciences, University of Ghana, Legon, Ghana.
  • 5. Department of Pharmacology, Faculty of Pharmacy and Pharmaceutical Sciences, College of Health Sciences, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana.
  • 6. Manhyia Government Hospital, Kumasi, Ghana.
  • 7. Department of Clinical Microbiology, School of Medicine and Dentistry, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana. [email protected].
PMID: 34078370 DOI: 10.1186/s12906-021-03326-x
Abstract

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.

Keywords
Anti-cancer; Carcinogenesis; Cryptolepine; Hepatoma; IL-6/STAT3.
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