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Cytotoxicity of Ficus Crocata Extract on Cervical Cancer Cells and Protective Effect against Hydrogen Peroxide-Induced Oxidative Stress in HaCaT Non-Tumor Cells.

ABSTRACT: Oxidative stress causes several chronic diseases including cancer. Some chemotherapeutic agents are not selective against tumor cells, causing oxidative stress in non-tumor cells. This study aimed to evaluate the cytotoxic effect of acetone extract of Ficus crocata(Miq.) Mart. ex Miq. (F. crocata) leaves (Ace-EFc) on cervical cancer cells, as well as its protective effect on hydrogen peroxide (H₂O₂)-induced lipoperoxidation and cytotoxicity in non-tumor HaCaT cells. Antioxidant activity was determined using the DPPH and ABTS radicals. Cell viability and lipoperoxidation were determined with MTT and 1-methyl-2-phenylindole assays, respectively. A model of H₂O₂-induced cytotoxicity and oxidative damage in HaCaT cells was established. HaCaT cells were exposed to the extract before or after exposure to H₂O₂, and oxidative damage and cell viability were evaluated. Ace-EFc inhibited the DPPH and ABTS radicals and showed a cytotoxic effect on SiHa and HeLa cells. Furthermore, the extract treatment had a protective effect on hydrogen peroxide-induced lipoperoxidation and cytotoxicity, avoiding the increase in MalonDiAldehyde (MDA) levels and the decrease in cell viability (p < 0.001). These results suggest that the metabolites of F. crocata leaves possess antioxidant and cytoprotective activity against oxidative damage. Thus, they could be useful for protecting cells from conditions that cause oxidative stress.

SUBMITTER: De la Cruz-Concepcion B

PROVIDER: S-EPMC7835743 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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Cytotoxicity of Ficus Crocata Extract on Cervical Cancer Cells and Protective Effect against Hydrogen Peroxide-Induced Oxidative Stress in HaCaT Non-Tumor Cells.

De la Cruz-Concepción Brenda B Espinoza-Rojo Mónica M Álvarez-Fitz Patricia P Illades-Aguiar Berenice B Acevedo-Quiroz Macdiel M Zacapala-Gómez Ana E AE Navarro-Tito Napoleón N Jiménez-Wences Hilda H Torres-Rojas Francisco I FI Mendoza-Catalán Miguel A MA

Plants (Basel, Switzerland) 20210119 1

Oxidative stress causes several chronic diseases including cancer. Some chemotherapeutic agents are not selective against tumor cells, causing oxidative stress in non-tumor cells. This study aimed to evaluate the cytotoxic effect of acetone extract of Ficus crocata (Miq.) Mart. ex Miq. (F. crocata) leaves (Ace-EFc) on cervical cancer cells, as well as its protective effect on hydrogen peroxide (H2O2)-induced lipoperoxidation and cytotoxicity in non-tumor HaCaT ...[more]

PMID: 33478134

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Project description:Triple-negative breast cancer (TNBC) is the most aggressive breast cancer subtype due to its greater invasive capacity and non-response to hormone therapy. Several species of the Ficus genus have been used as an alternative to traditional medicine against malignant diseases. Previously, leaf extracts from Ficus crocata (Miq.) Mart. ex Miq. (F. crocata) showed antiproliferative activity in vitro against breast and cervical tumor cells without having a cytotoxic effect on non-tumor cell lines. The purpose of the study was to evaluate the effect of hexane (Hex-EFc), dichloromethane (Dic-EFc), and acetone (Ace-EFc) extracts from F. crocata on the proliferative and invasive capacity of breast cancer cells MCF-7 and MDA-MB-231. Materials and methods The phytochemical profile was carried out by gas chromatography-mass spectrometry (GC-MS). Cell proliferation, migration, and invasion were determined by MTT, wound closure, and transwell assays, respectively. MMPs activity was analyzed using gelatin zymography, and fluorescence microscopy was used to visualize F-actin distribution. Results Hex-EFc, Dic-EFc, and Ace-EFc showed cytotoxic activity on MDA-MB-231 tumor cells and, to a lesser extent, on MCF-7 cells, without presenting cytotoxicity at the same concentrations in MCF-10A non-tumor cells. Dic-EFc and Ace-EFc (5–10 μg/mL) reduced the migration capacity of MCF-7 and MDA-MB-231 cells. Interestingly, exposure to Dic-EFc and Ace-EFc (5–10 μg/mL) inhibited the invasive ability of MDA-MB-231 cells, reducing the secretion and activity of MMP-2 and MMP-9, as well as the F-actin distribution. Conclusions Dic-EFc and Ace-EFc at low concentrations decreased breast cancer cell proliferation and invasiveness, mainly of MDA-MB-231 cells. The above supports the potential use of compounds from leaf extracts of F. crocata in neoadjuvant therapy to reduce the progression of breast cancer tumors, mainly triple-negative tumors. Graphical abstract Image 1 Highlights • F. crocata extracts induce a cytotoxic effect on breast cancer cells.• Ace-EFc and Dic-EFc inhibit the migration of breast cancer cells.• Ace-EFc and Dic-EFc reduce the invasion capacity and secretion of MMP-2 and MMP-9 in MDA-MB-231 cells.• Ace-EFc and Dic-EFc reduce actin polymerization and probably EMT in MDA-MB-231 cells. Triple-negative breast cancer; Ficus; Moraceae; Cell invasion; Complementary therapy.

Project description:Gall (Galla Rhois [GR]) is known to have antibacterial, anti-inflammatory, antimetastatic, and anti-invasion activities and exert hepatoprotective effects. However, the hepatoprotective effects of gallotannin-enriched GR (GEGR) and their mechanisms have not yet been investigated.The potential protective effect of GEGR against hepatotoxicity induced by hydrogen peroxide (H2O2) was investigated.Changes in cell viability, apoptosis protein expression, and reactive oxygen species (ROS) generation were determined in HepG2 cells that were pretreated with four different concentrations of GEGR (6.25-50 μg/ml) for 24 h before H2O2 exposure.GEGR consisted of gallotannin (69.2%), gallic acid (26.6%), and methyl gallate (4.2%) and showed remarkable 2,2-diphenyl-1-picrylhydrazyl scavenging activity (inhibitory concentration 50% = 0.212 μg/ml). The lethal dose 50% and effective dose 50% values for the response of HepG2 cells to GEGR were determined to be 178 and 6.85 μg/ml, respectively. Significant reductions in the immunofluorescence intensity indicating apoptosis were also detected in the nuclei of HepG2 cells stained with 4',6-diamidino-2-phenylindole and Annexin V after GEGR treatment. The Bax/Bcl-2 ratio and active caspase-3 level were higher in H2O2 + vehicle-treated cells. However, these levels gradually decreased to those of the No-treated group in the GEGR pretreated group even though little or no decrease was observed in response to low GEGR concentrations. Furthermore, the GEGR pretreated group showed a reduced level of 2',7'-dichlorofluorescein diacetate stained cells, indicating ROS generation relative to the H2O2 + vehicle-treated group.The results of this study provide strong evidence that GEGR can prevent cell death induced by H2O2 in HepG2 cells through the induction of antioxidant conditions.The gallotannin (69.2%), gallic acid (26.6%), and methyl gallate (4.2%) are the main constituents of water extracts of GRGEGR was more potent in DPPH scavenging, and gallotannin contributes to this extract activityGEGR significantly reduced the increase of apoptosis, Bax/Bcl-2 ratio, and active caspase-3 level after H2O2 treatmentGEGR pretreatment showed protection against H2O2-induced ROS production in DCFH-DA staining analysis. Abbreviations used: COX: Cyclooxygenase; DAPI: 4',6-diamidino-2-phenylindole; DMSO: Dimethyl sulfoxide; DPPH: 2,2-diphenyl-1-picrylhydrazyl; GEGR: Gallotannin-enriched Galla Rhois; GR: Galla Rhois; HPLC: High-performance liquid chromatography; H2O2: Hydrogen peroxide; MMP: Metallopeptidase; MTT: 3-(4,5 dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide; ROS: Reactive oxygen species; UV-Vis: Ultraviolet-visible.

Dataset Information

Cytotoxicity of Ficus Crocata Extract on Cervical Cancer Cells and Protective Effect against Hydrogen Peroxide-Induced Oxidative Stress in HaCaT Non-Tumor Cells.

Publications

Cytotoxicity of Ficus Crocata Extract on Cervical Cancer Cells and Protective Effect against Hydrogen Peroxide-Induced Oxidative Stress in HaCaT Non-Tumor Cells.

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