WNT signaling is critical in regulating stem cell behavior and promoting neoplastic transformation in several cancers. A recent study from Ruiz i Altaba's group uncovered a novel WNT inhibitor (Withanolide F) which produces long-term repression of WNT-TCF targets, and is paralleled by changes in the epigenetic landscape in different cancer cells, leading to the possibility that the drug's effect on WNT signaling occurs via epigenetic alterations. We embarked on our analysis in downregulating specific genes which could be potentially involved in its epigenetic modulation and test if the individual gene silencing could recapitulate Withanolide F effects on WNT response. However, our results show that SMARCAL1 knockdown in two primary colon cancer cells do not recapitulate the drug's effects, but generate changes in certain behaviors. Thus, SMARCAL1 knockdown can affect the epigenetic landscape on these cancer cells but does not appear to mimic the effect of Withanolide F treatment.