Induction of autophagy by polyphenolic compounds in cancer: A novel strategy to induce cell death and to treat cancer

Apoptosis (type I) and autophagy-associated cell death (type II) are both highly regulated forms of programmed cell death and play crucial roles in physiological processes such as the development, homeostasis and selective elimination of cells. Autophagy is an evolutionarily conserved lysosomal pathway for degrading cytoplasmic proteins, macromolecules, and organelles and functions as a survival pathway in response to nutrient and growth factor deprivation. If the process is induced excessively, autophagy leads to cell death. In contrast to apoptosis, cell death occurring with autophagy is caspase-independent and does not involve classic DNA laddering. Accumulating evidence suggests that cancer cells that are resistant to apoptosis can be killed by death associated with autophagy, providing an alternative cell death pathway to eliminate cancer cells. We and others found that natural polyphenolic compounds, such as rottlerin, resveratrol, curcumin, genistein, and quercetin can induce cell death associated with autophagy in a variety of cancer cells, including pancreatic, breast, glioma, colon, ovarian cancers and acute myeloid leukemia. More importantly, these compounds can enhance the effects of chemotherapy and reduce the required dose to induce cell death in cancer cells. In this chapter we will discuss the polyphenolic compounds and the mechanism by which they induce cell death occurring with autophagy in cancer cells and their potential as a novel strategy for the treatment of cancer.