Alpha mangostin inhibits proliferation, migration, and invasion of human breast cancer cells via STAT3 inhibition
Lakshmi Vineela Nalla, Anil Dharavath, Santosh Kumar Behera, Amit Khairnar
Abstract
Signal Transducer and Activator of Transcription 3 (STAT3) is an identified critical protein associated with the progression of cancer. Alpha mangostin (alpha-M), a powerful dietary xanthone found to have anti-cancer properties against various cancers. However, the precise mechanism of its anti-cancer activity is not fully understood. Therefore, the current work hypothesized that targeting STAT3 with alpha-M inhibits the migration, invasion, and proliferation of breast cancer cells. Firstly, we evaluated the binding affinity of alpha-M/STAT3 complex using molecular dynamic simulations (MDS) and further we determined the likely underlying mechanism of STAT3 through in-vitro experiments. alpha-M treatment affected the levels of STAT3 phosphorylation, hnRNP-A1, PKM2, and EMT markers. alpha-M stimulation in breast cancer cells also resulted in suppressed migratory and invasive behaviour. More importantly, the treatment also affected the Ki67 and BrdU positive cells. In summary, we found the anti-migratory and anti-proliferative actions of alpha-M in breast cancer cells via STAT3 inhibition. Also, the study significantly adds a new nutraceutical for therapeutic intervention of invasive breast cancer.