Withaferin A plays a significant role in the inhibition of several signal transduction pathways, such as Notch-1 signaling and the downregulation of pro-survival pathways, including Akt serine/threonine kinase (Akt)/nuclear factor-κB (NF-ĸB)/B-cell lymphoma 2 (Bcl-2) in colon cancer cell lines, and the suppression of the phosphorylation and translocation of suppressor of mothers against decapentaplegic 2/3 (Smad2/3) and NF-κB in cancer cells [22,23,24,25,26,27]. This evidence concerns the gene NOTCH1 and malignant colon neoplasm.