Cryptolepine, a plant-derived alkaloid, differentially regulates signal transduction pathways in human embryonic kidney (HEK293) cells

Patrick Narkwa; Seth Domfeh; Gordon  Awandare; Mohamed Mutocheluh

doi:10.4314/just.v41i3.1490

Dr. Patrick Williams Narkwa Department of Clinical Microbiology, School of Medicine and Dentistry, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana https://orcid.org/0000-0003-2490-7902
Dr. Seth Agyei Domfeh Department of Biochemistry and Biotechnology, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana https://orcid.org/0000-0002-1689-7663
Prof. Gordon Awandare West African Centre for Cell Biology of Infectious Pathogens, Department of Biochemistry, Cell and Molecular Biology, University of Ghana, Legon https://orcid.org/0000-0002-8793-3641
Prof. Mohamed Mutocheluh Department of Clinical Microbiology, School of Medicine and Dentistry, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana https://orcid.org/0000-0002-1396-5085

DOI: https://doi.org/10.4314/just.v41i3.1490

Keywords: Cryptolepine, Cell signalling, Progesterone receptor, IRF1, STAT3, HIF-1α

Abstract

Cryptolepine is the main alkaloid in the medicinal plant Cryptolepis sanguinolenta. This plant- derived alkaloid has innumerable pharmaco-biological properties, including anti-microbial, anti- hyperglycaemic and anti-inflammatory in diverse in vitro and in vivo systems. We have previously shown that cryptolepine differentially regulates signalling pathways in human hepatoma (HepG2) cells. Hence, this current study aimed to investigate the effects of cryptolepine on these pathways in human embryonic kidney (HEK293) cells to ascertain whether what we reported in the HepG2 cells is cell dependent. The Cignal Finder Multi-Pathway Reporter Array was used to screen the effects of cryptolepine on the pathways in the HEK293 cells. Next, some genes in the differentially regulated pathways were assessed using RT-qPCR. Cryptolepine up-regulated 9 pathways, including p53, IRF1 and PR, supported by increased IRF1 and PR transcripts. Contrarily, cryptolepine down-regulated 27 pathways, including STAT3, c-Myc and HIF-1α, bolstered by decreased HIF1-α and STAT3 transcripts. The regulations of the pathways in the HEK293 cells differed from those observed in the HepG2 cells. This study revealed that cryptolepine differentially regulates signalling pathways and regulates these pathways differently in diverse cells. The results from our studies support the pharmaco-biological effects of cryptolepine in different cells.

Author Biographies

Dr. Patrick Williams Narkwa, Department of Clinical Microbiology, School of Medicine and Dentistry, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana

Patrick is a Lecturer of Virology and Immunology at the Department of Clinical Microbiology at Kwame Nkrumah University of Science and Technology (KNUST), Kumasi. He studied Biological Sciences at the undergraduate level and had his MSc and PhD in Clinical Microbiology at KNUST. His PhD was focused on understanding the role of aflatoxin B1 in modulating the type 1 interferon response. He was awarded the Leverhulme Royal Society Africa Award-Postdoctoral Fellowship (£ 40,000.00) in 2019 to investigate the interactions between aflatoxin B1 and hepatitis B virus: effects on type 1 interferon pathway. He also received research support ($ 25,000.00) from the West African Centre of Cell Biology and Infectious Pathogens (WACCBIP), University of Ghana, in 2017 to investigate the effects of cryptolepine on human cancer pathways.

Dr. Seth Agyei Domfeh, Department of Biochemistry and Biotechnology, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana

Seth is a Lecturer in the Department of Biochemistry and Biotechnology, Kwame Nkrumah University of Science and Technology (KNUST), Kumasi. Seth holds an MPhil in Immunology from KNUST and a PhD in Molecular Cell Biology of Infectious Diseases from the University of Ghana, Legon. Seth’s areas of specialisation are immunology and molecular cell biology, with an interest in understanding the mechanisms underlying malaria parasite gametocytogenesis and hepatocellular carcinogenesis (HCC). Also, Seth focuses on discovering natural products with gametocytocidal activities and immune-boosting properties against hepatitis B virus and HCC.

Prof. Gordon Awandare, West African Centre for Cell Biology of Infectious Pathogens, Department of Biochemistry, Cell and Molecular Biology, University of Ghana, Legon

Gordon is a Professor of Biochemistry, Cell and Molecular Biology, and the Pro Vice-Chancellor (Academic and Student Affairs) at the University of Ghana, Legon. Also, he is the Founding Director of the West African Centre for Cell Biology of Infectious Pathogens (WACCBIP). He holds an MPhil in Biochemistry from the University of Ghana, Legon and a PhD in Infectious Diseases and Microbiology from the University of Pittsburgh, USA. His area of specialisation is malaria immunology, focusing on the pathogenesis of Plasmodium falciparum malaria in children.

Prof. Mohamed Mutocheluh, Department of Clinical Microbiology, School of Medicine and Dentistry, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana

Mohamed is an Associate Professor at the Department of Clinical Microbiology, Kwame Nkrumah University of Science and Technology, Kumasi. He holds an MSc in Molecular Medical Microbiology from the University of Nottingham, UK, and an MPhil and a PhD in Immunology and Infection from the University of Birmingham, UK. Mohamed’s areas of specialisation are virology, immunology and cancer biology, focusing on translational research related to microbial pathogens and immunity to microbial diseases, with a keen interest in oncogenic viruses and mycotoxins.