Inhibition of NF-κB signalling pathway by methanol extract of fruit pericarp of Garcinia gummi-gutta in inflammatory breast cancer with triple negative phenotype

Abstract

In humans, triple negative breast cancer (TNBC) is a highly truculent form of mammary gland cancer that connexions clinical, pathological and molecular patterns of disease with canine inflammatory mammary carcinoma (IMC). Inflammatory breast cancer with TNBC phenotype has shoddier prognosis and mediocre outcome when juxtaposed with non-inflammatory breast cancer (IBC) with TNBC phenotype. This demands the need for effective therapeutics and targets for its treatment which is currently lacking. Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), a major regulator of inflammation is a potential therapeutic target in TNBC. The present study was instigated to appraise the anticancer properties of methanol extract of Garcinia gummi-gutta (MGG) in MDA-MB-231, a triple negative breast carcinoma cell line. The extract was gaged for its cytotoxic property in tumour necrotic factor- alpha (TNF-α) stimulated MDA-MB-231 cell line, where we obtained a half maximal inhibitory concentration (IC₅₀) value of 50.3 μg/mL. On acridine orange/ ethidium bromide staining, MDA-MB-231 cells treated with the extract unveiled marked morphological and nuclear alterations which were characteristics of apoptosis. In the gene expression study, NF-κB expression was down-regulated in the MGG treated TNF-α stimulated MDA-MB-231 cell line. In conclusion, our present study divulged that the MGG exhibited a concentration dependent cytotoxic activity in TNF-α stimulated MDA-MB-231 breast carcinoma cell lines. Furthermore, our study revealed that the extract was effective in inhibiting the NF-κB signalling pathway which makes it a pledging source for isolating therapeutic molecules for the treatment of inflammatory breast cancer with TNBC phenotype.