Deciphering the anti-cancer efficacy of azadirachta indica and its role in re-expression of e-cadherin in breast cancer via snail and hdacs

Abstract

Neem (Azadirachtaindica), considered natural drug house, has been a source of numerous modern drugs in both developed and developing countries across globe. The anti-cancer components of Neem comprising of azadirachtin, nimbolide, quercetin, limonin, glucopyranoside, azadirone, and deoxonimbolide are targeted to the culprit enzymes accountable for tumor formation, subsequently combating cancer. Cancer, especially breast cancer has been responsible for the drastic mortality rate among all females. Cancer is characterized by genetic and epigenetic aberrations. These epigenetic aberrations are reversible thus accounting for the restoration of the functionality of tumor suppressor gene. In our study, we have carried out an effort towards checking the effect of neem extracts towards restoring the expression of tumor suppressor gene, E-cadherin (CDH1) via Snail and histone deacetylases (HDACs) in breast cancer cells MDA MB 231.Histone acetylation erasers, HDACs are the epigenetic manipulators playing a crucial role in silencing of tumor suppressor genes concerned with cancer initiation and progression. There are several HDAC inhibitors available but they have higher toxicity. Here, we have considered both the ethanolic and methanolic extracts of neem leaves (EENL and MENL), as they have been reported to be more effective than the aqueous extracts. The higher total phenolic content of EENL indicates its higher anti-oxidant property, which accounts for its anti-cancer potential. Also the cytotoxicity, anti-proliferative, apoptotic and anti-migratory potential of EENL are demonstrated to be more than that of MENL. Moreover, EENL restores more efficiently the expression of CDH1 and causes an enhanced transcript level of HDAC1 and HDAC2. Thus, it can be concluded that EENL may have HDAC inhibitory activity than MENL. Further research in this concern will shed more light on the HDAC inhibitory property of EENL and MENL on breast cancer cells.