Antiproliferative activity and phenotypic modification induced by selected Peruvian medicinal plants on human hepatocellular carcinoma Hep3B cells

Autor: Cedric Lavergne, Jean Edouard Gairin, Valérie Jullian, Maëlle Carraz, Geneviève Bourdy, Michel Wright, Mercedes Gonzales de la Cruz
Přispěvatelé: Pharmacochimie et Biologie pour le Développement (PHARMA-DEV), Institut de Recherche pour le Développement (IRD)-Institut de Chimie de Toulouse (ICT-FR 2599), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC), University Ricardo Palma = Universidad Ricardo Palma (URP), Institut de Recherche pour le Développement (IRD)-Institut de Chimie de Toulouse (ICT), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)
Jazyk: angličtina
Rok vydání: 2015
Předmět:
Zdroj: Journal of Ethnopharmacology
Journal of Ethnopharmacology, Elsevier, 2015, 166, pp.185-199. ⟨10.1016/j.jep.2015.02.028⟩
Journal of Ethnopharmacology, 2015, 166, pp.185-199. ⟨10.1016/j.jep.2015.02.028⟩
ISSN: 0378-8741
DOI: 10.1016/j.jep.2015.02.028⟩
Popis: Ethnopharmacological relevance The high incidence of human hepatocellular carcinoma (HCC) in Peru and the wide use of medicinal plants in this country led us to study the activity against HCC cells in vitro of somes species used locally against liver and digestive disorders. Materials and methods Ethnopharmacological survey: Medicinal plant species with a strong convergence of use for liver and digestive diseases were collected fresh in the wild or on markets, in two places of Peru: Chiclayo (Lambayeque department, Chiclayo province) and Huaraz (Ancash department, Huaraz province). Altogether 51 species were collected and 61 ethanol extracts were prepared to be tested. Biological assessment : All extracts were first assessed against the HCC cell line Hep3B according a 3-step multi-parametric phenotypic assay. It included 1) the evaluation of phenotypic changes on cells by light microscopy, 2) the measurement of the antiproliferative activity and 3) the analysis of the cytoskeleton and mitosis by immunofluorescence. Best extracts were further assessed against other HCC cell lines HepG2, PLC/PRF/5 and SNU-182 and their toxicity measured in vitro on primary human hepatocytes. Results Ethnopharmacological survey: Some of the species collected had a high reputation spreading over the surveyed locations for treating liver problems, i.e. Baccharis genistelloides, Bejaria aestuans, Centaurium pulchellum, Desmodium molliculum, Dipsacus fullonum, Equisetum bogotense, Gentianella spp., Krameria lapacea, Otholobium spp., Schkuhria pinnata, Taraxacum officinale . Hep3B evaluation: Fourteen extracts from 13 species ( Achyrocline alata , Ambrosia arborescens , Baccharis latifolia , Hypericum laricifolium , Krameria lappacea , Niphidium crassifolium , Ophryosporus chilca , Orthrosanthus chimboracensis , Otholobium pubescens , Passiflora ligularis , Perezia coerulescens , Perezia multiflora and Schkuhria pinnata ) showed a significant antiproliferative activity against Hep3B cells (IC 50 ≤ 50 µg/mL). This was associated with a lack of toxicity on primary human hepatocytes in vitro . Immunofluorescence experiments on Hep3B cells showed that crude extracts of Schkuhria pinnata and Orthrosanthus chimboracensis could block Hep3B cells in mitosis with an original phenotype. Crude extracts of Perezia coerulescens , Perezia multiflora , Achyrocline alata , Ophryosporus chilca , Otholobium pubescens and Hypericum laricifolium could modify the overall microtubule cytoskeletal dynamics of Hep3B cells in interphase by an original mechanism. Conclusions Our method allowed us to select 9 extracts which displayed antiproliferative activities associated with original cellular phenotypes on Hep3B cells, regarding known microtubule-targeting drugs. Both chemical and cellular studies are ongoing in order to elucidate natural compounds and cellular mechanisms responsible of the activities described.
Databáze: OpenAIRE
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