Roles of Autophagy Induced by Natural Compounds in Prostate Cancer

Abstract

Autophagy is a homeostatic mechanism through which intracellular organelles and proteins are degraded and recycled in response to increased metabolic demand or stress. Autophagy dysfunction is often associated with many diseases, including cancer. Because of its role in tumorigenesis, autophagy can represent a new therapeutic target for cancer treatment. Prostate cancer (PCa) is one of the most common cancers in aged men. The evidence on alterations of autophagy related genes and/or protein levels in PCa cells suggests a potential implication of autophagy in PCa onset and progression. The use of natural compounds, characterized by low toxicity to normal tissue associated with specific anticancer effects at physiological levels in vivo, is receiving increasing attention for prevention and/or treatment of PCa. Understanding the mechanism of action of these compounds could be crucial for the development of new therapeutic or chemopreventive options. In this review we focus on the current evidence showing the capacity of natural compounds to exert their action through autophagy modulation in PCa cells.

Resveratrol induces autophagic apoptosis via the lysosomal cathepsin D pathway in human drug‑resistant K562/ADM leukemia cells

“…Various antitumor effects of Res have been described previously, including the inhibition of DNA polymerase, protein kinase C, cyclooxygenase-2 or interleukin-6 activities, and the suppression of transcription factors such as nuclear factor-κB (4,11,12,21,22). The present study revealed that Res increased autophagosome formation, decreased cell viability and induced apoptotic death in drug-resistant K562/ADM cells.…”

“…Res has been shown to induce cell death through various mechanisms in different cancer cell lines (2,11,12,19). Various antitumor effects of Res have been described previously, including the inhibition of DNA polymerase, protein kinase C, cyclooxygenase-2 or interleukin-6 activities, and the suppression of transcription factors such as nuclear factor-κB (4,11,12,21,22).…”

“…In the present study, western blotting results revealed that Res significantly increased the expression levels of Bax and decreased those of Bcl-2. The interaction of beclin 1 with Bcl-2 in the cytosolic compartment may increase efficient Bax translocation to mitochondria, leading to permeabilization of the mitochondrial membrane, cytochrome c release and activation of a caspase cascade, and finally, initiation of caspase-dependent cell death (2,10,11).…”

“…Yan et al (10) reported that Res not only induced leukemia cell apoptosis and erythroid differentiation, but also autophagy. A previous report has indicated that Res induces autophagy in different cancer cell lines via either a pro-survival or pro-death mechanism (11 have demonstrated that Res increases the sensitivity of malignancies, including melanoma, prostate and non-small lung cancer, to chemotherapy (12,13). Although Res is known to induce apoptosis and autophagy in different types of tumor cells, few studies have explored the effects of Res-induced autophagy and its association with apoptosis in drug-resistant leukemia cells.…”

Green Tea Catechins for Prostate Cancer Prevention: Present Achievements and Future Challenges

“…Normally autophagy is constitutively active at low levels to guarantee cellular homeostasis, but it can be strongly induced in stressful conditions when this process seems to act primarily as a cellular protective response [135]. The effects of EGCG on autophagy seem to be dependent on concentration used, cell type and stress conditions.…”