Food and medicinal plants from Nigeria with anti-Helicobacter pylori activities induce apoptosis in colon and gastric cancer cell lines

Abstract

Background: Food and medicinal plants are used traditionally in Nigeria to treat gastrointestinal (GI) disorders such as gastritis, peptic ulcer disease and GI-related cancers. We have previously reported that specific extracts of Nigerian food and medicinal plants inhibited the growth of Helicobacter pylori, a bacterium known to cause peptic ulcer disease, as well as gastric and colon cancer. Objective: To determine the effects of three food plants, namely Anogeissus leiocarpus (DC.) Guill. & Perr.  (African birch, Combretaceae), Terminalia glaucescens Planch ex Benth. (Nigerian chewing sticks, Combretaceae) and Dillenia indica L. (Elephant apple, Dilleniaceae) used in Nigeria for the treatment of GI disorders and cancer in six colon and gastric cancer cell lines, and two non-cancerous cell lines. Methods: Cancer cells were grown in appropriate media and CellTiter-Glo® 2.0 and ApoTox-Glo™ Triplex assays were used to measure cell growth and apoptosis in SW480, SW620, HCT116, Caco2 cell lines, as well as  AGS and NCI-N87 gastric cancer cells. Caspase-Glo® 3/7, and Caspase-Glo® 8 were used to determine caspase activities and apoptosis. Gene expression was measured using quantitative PCR.Results: The methanol extract of A. leiocarpus roots inhibited the growth of HCT-116, SW480 and SW620 colon cancer cells (IC50 of 15.8, 10.0, and 20.8 µg/mL, respectively), but weakly active in the AGS and NCI-N87 cells (IC50 77.0 and >100 µg/mL respectively). The T. glaucescens extract was weakly active in HCT-116 cells (IC50 64.9 µg/ml) and AGS cells (52.2 µg/ml). The D. indica extract was active in SW480 (IC50 15.8 µg/mL), and weakly active in Caco2 (IC50 35.2 µg/mL) and HCT-116 (IC50 53.2 µg/mL). In HCT-116 cells, A. leiocarpus root extract and its aqueous partition increased caspase 8 activity, as well as mRNA expression of p53, while expression of Bcl-2 and HDAC1 mRNA was reduced. Bioassay guided fractionation of the aqueous partition led to the isolation and identification of the known compound methyl gallate.Conclusions: These data suggest that the Nigerian food plants with anti-Helicobacter pylori activities increase the expression of the tumor suppressor p53 and inhibit HDAC1, thereby inducing apoptosis in HCT-116 colon cancer cells.Running Title: Inhibitory Effects of Nigerian food plants on GIT CancersKeywords: African birch, AGS, Apoptosis, Anogeissus leiocarpus, Dillenia indica, Elephant apple, Terminalia glaucescens, Nigerian chewing sticks, HCT-116, SW480, SW620