Polyphenol-mediated autophagy in cancer: Evidence of in vitro and in vivo studies

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

Polyphenol-Mediated Autophagy in Cancer: Evidence of In Vitro and In Vivo Studies.

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

Basic fibroblast growth factor modifies the interactions between endothelial cells/fibronectin: Implications for progression of AIDS- associated Kaposi's sarcoma

Kaposi's sarcoma (KS) is an angioproliferative disease frequently arising in HIV-1 infected individuals (AIDS-KS). Previous studies indicated that cells derived from AIDS-KS lesions (AIDS-KS cells) produce the angiogenic basic fibroblast growth factor (bFGF) and release it in a biologically active form. Here we show that this extracellular bFGF increases in endothelial cells the expression of fibronectin (FN)-degrading proteases, such as stromelysin-1, stromelysin-3 and collagenase IV, and of the FN- binding integrin α5β1. Consequently, bFGF produced by AIDS-KS cells improves the capability of endothelial cells to migrate toward FN digested and cleaved from blood vessel basement membrane and perivascular stroma by proteases. These results suggest a mechanism for two phenomena that characterize AIDS-KS lesions and that are fundamental for its progression: the invasivity of endothelial cells and the abnormal angiogenesis

Defective expression of neutrophil membrane proteins in patients with rheumatoid arthritis

At least 14 iodinated proteins can be distinguished by SDS polyacrylamide gel electrophoresis followed by autoradiography in the membrane of intact human neutrophils. Neutrophils from patients suffering from rheumatoid arthritis show a modified expression of 4 outer membrane proteins. Three polypeptide components of the 30, 50 and 130 K were decreased by 95%, while the 120 K component dramatically increased. The possible relationship between the altered cell sensitivity and the defective expression of membrane proteins is discussed

Multifaceted Role of the Placental Growth Factor (PlGF) in the Antitumor Immune Response and Cancer Progression.

The sharing of molecules function that affects both tumor growth and neoangiogenesis with cells of the immune system creates a mutual interplay that impairs the host's immune response against tumor progression. Increasing evidence shows that tumors are able to create an immunosuppressive microenvironment by recruiting specific immune cells. Moreover, molecules produced by tumor and inflammatory cells in the tumor microenvironment create an immunosuppressive milieu able to inhibit the development of an efficient immune response against cancer cells and thus fostering tumor growth and progression. In addition, the immunoediting could select cancer cells that are less immunogenic or more resistant to lysis. In this review, we summarize recent findings regarding the immunomodulatory effects and cancer progression of the angiogenic growth factor namely placental growth factor (PlGF) and address the biological complex effects of this cytokine. Different pathways of the innate and adaptive immune response in which, directly or indirectly, PlGF is involved in promoting tumor immune escape and metastasis will be described. PlGF is important for building up vascular structures and functions. Although PlGF effects on vascular and tumor growth have been widely summarized, its functions in modulating the immune intra-tumoral microenvironment have been less highlighted. In agreement with PlGF functions, different antitumor strategies can be envisioned

EVIDENCE FOR GLYCOPROTEIN ABNORMALITY IN PLATELETS FROM PATIENTS WITH MAY-HEGGLIN ANOMALY

Protein analysis on SDS-polyacrylamide gel electrophoresis (PAGE) has been used to study the glycoprotein pattern of the blood platelets of four members from a family affected by May-Hegglin anomaly. N,N'diallyltartardiamide (DATD) cross-linked gel electrophoresis was shown to improve the glycoprotein pattern resolution, although with the lactoperoxidase-iodination the glycoprotein characterization of May-Hegglin platelets overlapped the normal. With the immunoprecipitation the specific antiserum precipitated all the five major fractions of normal membrane glycoproteins, but it was shown to react quite poorly with the component V of the May-Hegglin glycoprotein pattern. Thus it could be argued that the component V is present on the surface of May-Hegglin platelets, but with different antigenic properties, which may be related to a change of the glycoproptein stereochemical set. Therefore it could be suggested that the obbserved antigenic alteration of fraction V may contribute to explain the bleeding occasionally occuring in some patients affected by May-Hegglin anomaly