1. Gallic acid indanone and mangiferin xanthone are strong determinants of immunosuppressive anti-tumour effects of Mangifera indica L. bark in MDA-MB231 breast cancer cells.
- Author
-
García-Rivera D, Delgado R, Bougarne N, Haegeman G, and Berghe WV
- Subjects
- Blotting, Western, Cell Line, Tumor, Cell Survival drug effects, Electrophoretic Mobility Shift Assay, Female, Humans, Immunosuppressive Agents pharmacology, Mangifera chemistry, Plant Bark chemistry, Reverse Transcriptase Polymerase Chain Reaction, Signal Transduction drug effects, Antineoplastic Agents pharmacology, Breast Neoplasms metabolism, Gallic Acid analogs & derivatives, Gallic Acid pharmacology, Phytotherapy, Plant Extracts pharmacology, Xanthones pharmacology
- Abstract
Vimang is a standardized extract derived from Mango bark (Mangifera Indica L.), commonly used as anti-inflammatory phytomedicine, which has recently been used to complement cancer therapies in cancer patients. We have further investigated potential anti-tumour effects of glucosylxanthone mangiferin and indanone gallic acid, which are both present in Vimang extract. We observed significant anti-tumour effects of both Vimang constituents in the highly aggressive and metastatic breast cancer cell type MDA-MB231. At the molecular level, mangiferin and gallic acid both inhibit classical NFκB activation by IKKα/β kinases, which results in impaired IκB degradation, NFκB translocation and NFκB/DNA binding. In contrast to the xanthone mangiferin, gallic acid further inhibits additional NFκB pathways involved in cancer cell survival and therapy resistance, such as MEK1, JNK1/2, MSK1, and p90RSK. This results in combinatorial inhibition of NFκB activity by gallic acid, which results in potent inhibition of NFκB target genes involved in inflammation, metastasis, anti-apoptosis and angiogenesis, such as IL-6, IL-8, COX2, CXCR4, XIAP, bcl2, VEGF. The cumulative NFκB inhibition by gallic acid, but not mangiferin, is also reflected at the level of cell survival, which reveals significant tumour cytotoxic effects in MDA-MB231 cells. Altogether, we identify gallic acid, besides mangiferin, as an essential anti-cancer component in Vimang extract, which demonstrates multifocal inhibition of NFκB activity in the cancer-inflammation network., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)
- Published
- 2011
- Full Text
- View/download PDF