Despite increased use of early detection methods and more aggressive treatment strategies, the worldwide incidence of
colorectal cancer is still on the rise. Consequently, it remains urgent to identify novel agents with enhanced efficacy in prevention and/or therapeutic protocols. Our studies focused on the use of
Plumbagin, a natural
phytochemical that showed promising results against other
tumor types, to determine its effectiveness in blocking the proliferation and survival of
colon cancer cells in experimental protocols mimicking the environment in primary
tumors (attached culture conditions) and in
circulating tumor cells (unattached conditions). Under both experimental settings, exposure of HCT116 cells to
Plumbagin concentrations in the low micromolar range resulted in cell cycle arrest at the G1 phase, apoptosis via the mitochondrial cell death pathway, and increased production of
reactive oxygen species. The cell cycle effects were more noticeable in attached cells, whereas the induction of cell death was more evident in unattached cells. These effects were consistent with the nature and the magnitude of the alterations induced by
Plumbagin on the expression levels of a set of
proteins known to play key roles in the regulation of cell cycle dynamics, apoptosis mechanisms and cell proliferation. In light of its previously reported lack of toxicity on normal colon cells and the striking anti-survival effect on
colon cancer cells observed in our study,
Plumbagin should be considered a promising
drug for the treatment of
colon cancer.