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Title
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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
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Author
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Abstract
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| 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. |
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Language
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English
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Source (journal)
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Cancer letters. - Amsterdam
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Publication
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Amsterdam
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2011
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ISSN
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0304-3835
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DOI
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10.1016/J.CANLET.2011.02.011
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Volume/pages
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305
:1
(2011)
, p. 21-31
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ISI
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000290133600003
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Full text (Publisher's DOI)
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Full text (publisher's version - intranet only)
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