Extracts of Crinum latifolium inhibit the cell viability of mouse lymph oma cell line EL4 and induce activation of anti-tumour activity of macrophages in vitro |
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Authors: | Hoang-Yen T Nguyen Bach-Hue T Vo Lac-Thuy H Nguyen Jose Bernad Mohamad Alaeddine Agnes Coste Karine Reybier Bernard Pipy Françoise Nepveu |
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Institution: | 1. University of Medicine and Pharmacy of Ho Chi Minh City, 41 Dinh Tien Hoang street, District 1, Ho Chi Minh City, Vietnam;2. Université de Toulouse, UPS, UMR 152, PHARMA-DEV, 118 route de Narbonne, F-31062 Toulouse cedex 9, France;3. IRD, UMR 152, F-31062 Toulouse cedex 9, France |
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Abstract: | Ethnopharmacological relevanceCrinum latifolium L. (CL) leaf extracts have been traditionally used in Vietnam and are now used all over the world for the treatment of prostate cancer. However, the precise cellular mechanisms of the action of CL extracts remain unclear.Aim of the studyTo examine the effects of CL samples on the anti-tumour activity of peritoneal murine macrophages.Materials and methodsThe properties of three extracts (aqueous, flavonoid, alkaloid), one fraction (alkaloid), and one pure compound (6-hydroxycrinamidine) obtained from CL, were studied (i) for redox capacities (DPPH and bleaching beta-carotene assays), (ii) on murine peritoneal macrophages (MTT assay) and on lymphoma EL4-luc2 cells (luciferine assay) for cytotoxicity, (iii) on macrophage polarization (production of ROS and gene expression by PCR), and (iv) on the tumoricidal functions of murine peritoneal macrophages (lymphoma cytotoxicity by co-culture with syngeneic macrophages).ResultsThe total flavonoid extract with a high antioxidant activity (IC50=107.36 mg/L, DPPH assay) showed an inhibitory action on cancer cells. Alkaloid extracts inhibited the proliferation of lymphoma cells either by directly acting on tumour cells or by activating of the tumoricidal functions of syngeneic macrophages. The aqueous extract induced mRNA expression of tumour necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and interleukin 6 (IL-6) indicating differentiation of macrophages into pro-inflammatory M1 polarized macrophages. The total flavonoid, alkaloid extracts and an alkaloid fraction induced the expression of the formyl peptide receptor (FPR) on the surface of the polarized macrophages that could lead to the activation of macrophages towards the M1 phenotype. Aqueous and flavonoid extracts enhanced NADPH quinine oxido-reductase 1 (NQO1) mRNA expression in polarized macrophages which could play an important role in cancer chemoprevention. All the samples studied were non-toxic to normal living cells and the pure alkaloid tested, 6-hydroxycrinamidine, was not active in any of the models investigated.ConclusionsOur results indicate that CL extracts and alkaloid fraction (but not pure 6-hydroxycrinamidine) inhibit the proliferation of lymphoma cells in multiple pathways. Our results are in accordance with traditional usage and encourage further studies and in vivo assays. |
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Keywords: | CL Crinum latifolium ROS reactive oxygen species MTT 3-(4 5-dimethylthiazol-2-yl)-2 5-diphenyltetrazolium bromide PCR polymerase chain reaction DPPH 2 2-diphenyl-1-picrylhydrazyl M1 classically activated macrophages PBMC peripheral blood mononuclear cells |
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