title: African Lettuce (Launaea taraxacifolia) Displays Possible Anticancer Effects and Herb-Drug Interaction Potential by CYP1A2, CYP2C9, and CYP2C19 Inhibition.
abstract: Medicinal plants are part of the healthcare systems worldwide, especially in low- and middle-income countries. African lettuce (Launaea taraxacifolia) is cultivated extensively in Africa, from Senegal in the west to Ethiopia and Tanzania in the east, and in Southern Africa. Potential anticancer effects of L. taraxacifolia have been suggested, but little is known about putative molecular mechanisms or potential for herb-drug interactions through inhibition or induction of drug-metabolizing enzymes. We investigated the effects of crude aqueous extracts of L. taraxacifolia on growth kinetics and cell cycle progression of the WHC01 esophageal cancer cells. Antiproliferative and apoptotic effects were evaluated using the MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay and flow cytometry, while examining, in parallel, the genes regulating apoptosis and cell cycle in this cell culture model. In addition, we tested the inhibitory and enzyme kinetic effects of the aqueous L. taraxacifolia using recombinant human CYP450 isozyme model systems (CYP1A2, CYP2C9, and CYP2C19). L. taraxacifolia exhibited a significant growth inhibitory effect on the WHC01 cancer cells. Most cell cycle genes were downregulated. Cell cycle analysis showed a G0-G1 cell cycle arrest in WHC01 cells in the presence of L. taraxacifolia extract, accompanied by morphological changes. L. taraxacifolia extract treatment resulted in downregulation of expression levels of CYP1A2 (p < 0.0005) and CYP2C19 (p < 0.003) by 50-70%. L. taraxacifolia extract caused reversible and time-dependent inhibition of the recombinant CYP1A2, CYP2C9, and CYP2C19. This study provides new insights on possible anticancer effects of L. taraxacifolia, a widely used medicinal plant in parts of Africa and across the world especially by patients with cancer. Further mechanistic studies expanding on these observations would be timely and contribute to the field of global precision medicine that requires solid understanding of drug and herb molecular mechanisms of action and drug-herb interaction potentials, given the worldwide use of medicinal plants.
authors.affiliation: 1 Pharmacogenetics Research Group, Division of Human Genetics, Department of Pathology and Institute of Infectious Diseases and Molecular medicine, Faculty of Health Sciences, University of Cape Town , Cape Town, South Africa .|2 School of Medical Sciences, University of Cape Coast , Cape Coast, Ghana .
authors.forename: Nicholas E
authors.initials: NE
authors.lastname: Thomford
authors.affiliation: 1 Pharmacogenetics Research Group, Division of Human Genetics, Department of Pathology and Institute of Infectious Diseases and Molecular medicine, Faculty of Health Sciences, University of Cape Town , Cape Town, South Africa .
authors.forename: Buyisile
authors.initials: B
authors.lastname: Mkhize
authors.affiliation: 3 International Centre for Genetic Engineering and Biotechnology (ICGEB) , Cape Town, South Africa .|4 Division of Medical Biochemistry and Institute of Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town , Cape Town, South Africa .
authors.forename: Kevin
authors.initials: K
authors.lastname: Dzobo
authors.affiliation: 1 Pharmacogenetics Research Group, Division of Human Genetics, Department of Pathology and Institute of Infectious Diseases and Molecular medicine, Faculty of Health Sciences, University of Cape Town , Cape Town, South Africa .
authors.forename: Keleabetswe
authors.initials: K
authors.lastname: Mpye
authors.affiliation: 3 International Centre for Genetic Engineering and Biotechnology (ICGEB) , Cape Town, South Africa .|4 Division of Medical Biochemistry and Institute of Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town , Cape Town, South Africa .
authors.forename: Arielle
authors.initials: A
authors.lastname: Rowe
authors.affiliation: 3 International Centre for Genetic Engineering and Biotechnology (ICGEB) , Cape Town, South Africa .|4 Division of Medical Biochemistry and Institute of Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town , Cape Town, South Africa .
authors.forename: M Iqbal
authors.initials: MI
authors.lastname: Parker
authors.affiliation: 1 Pharmacogenetics Research Group, Division of Human Genetics, Department of Pathology and Institute of Infectious Diseases and Molecular medicine, Faculty of Health Sciences, University of Cape Town , Cape Town, South Africa .
authors.forename: Ambroise
authors.initials: A
authors.lastname: Wonkam
authors.affiliation: 1 Pharmacogenetics Research Group, Division of Human Genetics, Department of Pathology and Institute of Infectious Diseases and Molecular medicine, Faculty of Health Sciences, University of Cape Town , Cape Town, South Africa .
authors.forename: Michelle
authors.initials: M
authors.lastname: Skelton
authors.affiliation: 5 Division of Exercise Science and Sports Medicine, Department of Human Biology, Faculty of Health Sciences, University of Cape Town , Cape Town, South Africa .
authors.forename: Alison V
authors.initials: AV
authors.lastname: September
authors.affiliation: 1 Pharmacogenetics Research Group, Division of Human Genetics, Department of Pathology and Institute of Infectious Diseases and Molecular medicine, Faculty of Health Sciences, University of Cape Town , Cape Town, South Africa .
authors.forename: Collet
authors.initials: C
authors.lastname: Dandara
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D019388:Cytochrome P-450 CYP1A2 / Q000187:drug effects*; D065731:Cytochrome P-450 CYP2C19 / Q000187:drug effects*; D065729:Cytochrome P-450 CYP2C9 / Q000187:drug effects*; D041743:Herb-Drug Interactions; D006801:Humans; D007527:Isoenzymes; D018545:Lactuca / Q000737:chemistry*; D000071185:Pharmacogenomic Testing; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D010946:Plants, Medicinal; D011994:Recombinant Proteins
chemical_list: D000970:Antineoplastic Agents; D007527:Isoenzymes; D010936:Plant Extracts; D011994:Recombinant Proteins; C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9; C504573:CYP1A2 protein, human; C045793:CYP2C19 protein, human; D019388:Cytochrome P-450 CYP1A2; D065731:Cytochrome P-450 CYP2C19