Abstract
One of the hallmarks of cellular transformation is the altered mechanism of cell death. There are three main types of cell death, characterized by different morphological and biochemical features, namely apoptosis (type I), autophagic cell death (type II) and necrosis (type III). Autophagy, or self-eating, is a tightly regulated process involved in stress responses, and it is a lysosomal degradation process. The role of autophagy in cancer is controversial and has been associated with both the induction and the inhibition of tumor growth. Autophagy can exert tumor suppression through the degradation of oncogenic proteins, suppression of inflammation, chronic tissue damage and ultimately by preventing mutations and genetic instability. On the other hand, tumor cells activate autophagy for survival in cellular stress conditions. Thus, autophagy modulation could represent a promising therapeutic strategy for cancer. Several studies have shown that polyphenols, natural compounds found in foods and beverages of plant origin, can efficiently modulate autophagy in several types of cancer. In this review, we summarize the current knowledge on the effects of polyphenols on autophagy, highlighting the conceptual benefits or drawbacks and subtle cell-specific effects of polyphenols for envisioning future therapies employing polyphenols as chemoadjuvants.
Highlights
One of the hallmarks of cellular transformation is the altered mechanism of cell death
Miyamoto et al reported that phenoxodiol, a synthetic analogue of the plant isoflavone genistein with an improved anticancer efficacy (0.5–2 μg/mL), inhibited autophagy and X-linked inhibitor of apoptosis protein (XIAP), sensitizing ovarian clear cell carcinoma cells (KK cells) to cisplatin treatment [191]
The results showed that JNK-associated leucine zipper protein (JLP) protected against curcumin-induced cell death (40 μM), by activating autophagy and p38 MAPK [218]
Summary
One of the hallmarks of cellular transformation is the altered mechanism of cell death. Three main autophagic processes can occur depending on the way in which the components to be degraded are transferred to the lysosomes and are dependent on the type of material to be eliminated They are macroautophagy (MA), (generally called autophagy), endosomal microautophagy/ microautophagy (mA) and chaperon-mediated autophagy (CMA). The autophagic process consists of five steps that include induction (i), nucleation (ii), vesicle lengthening and maturation (iii), vesicle fusion (iv) and, degradation and recycling (v) This process is tightly regulated by the recruitment of autophagy-related (ATG) proteins and is normally repressed by the mechanistic target of rapamycin complex 1 (mTORC1). CMA is a HSPA8-dependent autophagic mechanism that relies mainly on LAMP2A-mediated cargo translocation across the lysosomal membrane, other forms of microautophagy can be LAMP-2A-independent [23]. Polyphenols possess many biological activities that are important for human health, including antimicrobial, antioxidant, anti-inflammatory, antiviral, anticancer, and immunomodulatory functions [34,36,54,55,56,57]
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