ABSTRACT
Despite the recent advancement of treatment strategies, cancer ranks 2nd among the causes of death globally. Phytochemicals have gained popularity as an alternate therapeutic strategy due to their nontoxic nature. Here, we have investigated the anticancer properties of guttiferone BL (GBL) along with four known compounds previously isolated from Allanblackia gabonensis. The cytotoxicity was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. The study was extended for the assessment of the effect of GBL in PA-1 cells apoptosis induction, cell cycle distribution, and change in mitochondrial membrane potential using flow cytometry, Western blot analysis, and real-time PCR. Among the five tested compounds, GBL displayed significant antiproliferative effects against all tested human cancer cells (IC50 < 10µM). Moreover, GBL exhibited no significant cytotoxicity towards normal ovarian epithelial cell line (IOSE 364) up to 50 µM. GBL induced sub-G0 cell cycle arrest and significant upregulation of cell cycle regulatory proteins of ovarian cancer cell PA-1. Furthermore, GBL induced its apoptosis as depicted by the accumulation of cells both at the early and late apoptotic phase in Annexin V/PI assay. In addition, it decreased the PA-1 mitochondrial membrane potential and promoted upregulation of caspase-3, caspase-9, and Bax and downregulation of Bcl-2. GBL also showed a dose-dependent inhibition of PA-1 migration. Altogether, this study reveals that guttiferone BL, studied herein for the first time, exhibits efficient antiproliferative activity by the induction of apoptosis through the mitochondrial-dependent pathway. Its investigation as a therapeutic agent against human cancers especially ovarian cancer should be envisaged.
Subject(s)
Apoptosis , Benzophenones , Fruit , Ovarian Neoplasms , Female , Humans , Fruit/chemistry , Ovarian Neoplasms/drug therapy , Benzophenones/pharmacology , Cell Line, TumorABSTRACT
Phytochemicals present in medicinal plants (herbs, shrubs, and trees) are endowed with high antimicrobial and antioxidant properties. The aim of this work was to study the chemical composition, antioxidant, and antifungal activities of Tristemma mauritianum, Crassocephalum bougheyanum, and Lavigeria macrocarpa. Chemical composition of the plant extracts was determined using standard methods. The antioxidant activities were performed using 2,2-diphenyl-1-picrylhydrazyl (DPPH), ferric reducing antioxidant power (FRAP), nitric oxide (NO), and hydroxyl (OH) scavenging assays. The antifungal activity of plant extracts and their combinations with antifungals was evaluated against eleven Candida spp. using the broth microdilution method by determining the minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC). The quantitative chemical analysis of the extracts of T. mauritianum, L. macrocarpa, and C. bougheyanum showed that they contain phenols, tannins, and flavonoids that vary according to the plant species and extracts. All the plant extracts presented promising antifungal (MIC = 64-2048 µg/mL) and antioxidant activities. The extract of T. mauritianum displayed the highest antifungal (MIC = 64-256 µg/mL) and antioxidant (IC50 = 19.052 ± 1.11 µg/mL) activities which can be explained by its high phenolic content. Interestingly, extracts of T. mauritianum, L. macrocarpa, and C. bougheyanum displayed synergistic effects (fractional inhibitory concentration index, FICI ≤ 0.5) with ketoconazole against clinical resistant isolates. The results of the present study demonstrate promising antifungal and antioxidant activities of the tested plants that are associated to their phenol, tannin, and flavonoid contents. Hence, extracts of T. mauritianum and L. macrocarpa could be deeply investigated as antifungal alone and in combination with conventional antifungal drugs to treat infections caused by Candida spp.
ABSTRACT
BACKGROUND: Recinodindron heudelotii (Euphorbiaceae) is a plant used in Africa, particularly in Cameroon to treat various ailments including bacterial infections. In this study, we evaluated the extracts of the leaves (RHL) and bark (RHB) of R. heudelotii for their antibacterial and antibiotic resistance modulating activities against 29 Gram-negative bacteria, including multidrug-resistant (MDR) phenotypes. METHODS: The broth micro-dilution assay was used to evaluate the antibacterial activity, and the antibiotic resistance modulating effects of the plant extracts. RESULTS: RHL displayed the most important spectrum of activity with minimal inhibitory concentrations (MICs) values ranging from 256 to 1024 µg/mL against 75.86% of the 29 tested bacteria strains while RHB was not active. RHL also showed killing effects with minimal bactericidal concentrations (MBCs) ranging from 256 to 1024 µg/mL. The activities of tetracycline and kanamycin associated with RHL were improved on 88.89% and 77.78% of the tested MDR bacteria, at MIC/2 at MIC/4 respectively, with 2 to 16-folds decreasing of MIC. This suggests the antibiotic resistance modulating effects of these antibiotics. CONCLUSION: The present study provides data indicating a possible use of the leaves extract of Recinodindron heudelotii alone or in association with common antibiotics in the fight against bacterial infections including those involving MDR bacteria.
