Evaluation of potential anticancer agents derived from Physalis peruviana (Poha)

Nuclear factor-κB (NF-κB) and signal transducer and activator of transcription 3 (Stat3) proteins are critical factors that regulate tumor processes. Associations between NF-κB and STAT3 plays integrated roles in promoting cancer development responses. Consequently, inhibitors of NF-κB and STAT3 might be useful as novel anticancer therapeutics. Bioassay-guided fractionation of the ethyl acetate from the aerial parts of Physalis peruviana (Solanaceae) led to the isolation of one new withanolide (withaperuvin S) along with six known withanolides (phyperunolides B, peruvianolide H, perulactone, physalactone, withaperuvin N, and 4β-hydroxywithanolide E). These isolated compounds were evaluated for cancer chemopreventive potential based on their ability to inhibit nitric oxide (NO) production and tumor necrosis factor (TNF-α)-induced NF-κB activity. Among them, five compounds inhibited TNF-α-induced NF-κB activity with IC₅₀ values in the range of 0.08 – 62µM. Four isolated compounds further inhibited nitric oxide production in lipopolysaccharide-activated murine macrophage RAW 264.7 cells, with IC₅₀ values in the range of 0.64 – 86µM. All compounds were evaluated for growth inhibitory activity with U251MG glioblastoma and MDA-MB-231 breast cancer cells harboring aberrantly active STAT3, compared with normal NIH3T3 mouse fibroblasts that show no evidence of activated STAT3. Among the isolates, 4β-Hydroxywithanolide E differentially inhibited the viability of all three cell lines, with IC₅₀ values 0.1, 0.1 and 0.6µM, respectively, showing a 6-fold preferential effects for tumor cells that harbor aberrantly-active STAT3.

Fig. 1