Anticancer potential of withanolides and its derivatives from Physalis peruviana (POHA)

Aberrantly active nuclear factor-κB (NF-κB) and signal transducer and activator of transcription (STAT3) protein are critical factors that regulate tumor processes. Convincing evidence shows the association between NF-κB and STAT3 plays integrated role in promoting cancer development. Consequently, inhibitors of NF-κB and STAT3 isolated from natural sources might be useful as novel anticancer therapeutics. Bioassay-guided fractionation of the organic extracts from both the aerial parts and fruits of Physalis peruviana (Pp) led to the isolation of a series of withanolides (WS) including a chlorinated withanolide. Among them, ten compounds inhibited TNF-α-induced NF-κB activity with IC₅₀ values in the range of 0.04 – 31.2µM. Seven isolated compounds inhibited nitric oxide (NO) production in lipopolysaccharide-activated murine macrophage RAW 264.7 cells with IC₅₀ values in the range of 0.2 – 44.6µM. The isolate, 4β-Hydroxywithanolide E, differentially inhibited the viability of all three cell lines, with 6-fold preferential effect against human tumor lines (U251MG and MDA-MB-231), with IC₅₀ values of 0.3 and 0.1, respectively, compared to effects on normal NIH-3T3, with IC₅₀ value of 0.6µM.