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

Authors
  • Domfeh, Seth A.1, 2
  • Narkwa, Patrick W.3
  • Quaye, Osbourne1, 2
  • Kusi, Kwadwo A.1, 2, 4
  • Awandare, Gordon A.1, 2
  • Ansah, Charles5
  • Salam, Alimatu6
  • Mutocheluh, Mohamed3
  • 1 University of Ghana, Legon, Ghana , Legon (Ghana)
  • 2 School of Biological Sciences, University of Ghana, Legon, Ghana , Legon (Ghana)
  • 3 School of Medicine and Dentistry, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana , Kumasi (Ghana)
  • 4 Noguchi Memorial Institute for Medical Research, College of Health Sciences, University of Ghana, Legon, Ghana , Legon (Ghana)
  • 5 Kwame Nkrumah University of Science and Technology, Kumasi, Ghana , Kumasi (Ghana)
  • 6 Manhyia Government Hospital, Kumasi, Ghana , Kumasi (Ghana)
Type
Published Article
Journal
BMC Complementary Medicine and Therapies
Publisher
BioMed Central
Publication Date
Jun 02, 2021
Volume
21
Issue
1
Identifiers
DOI: 10.1186/s12906-021-03326-x
Source
Springer Nature
Keywords
License
Green

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.

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