Procyanidins from Vitis vinifera seeds induce apoptotic and autophagic cell death via generation of reactive oxygen species in squamous cell carcinoma cells

Abstract

Procyanidins can inhibit cell proliferation and tumorigenesis and induce apoptosis in human skin, breast and prostate carcinoma cell lines. Squamous cell carcinoma (SCC) of the skin is a common form of keratinocytic or non-melanoma skin cancer and is a deadly disease with a poor prognosis due to the ineffectiveness of therapy. The present study aimed to determine whether grape seed proanthocyanidin (GSP) may regulate different modes of cell death in the human SCC12 cell line. The present study found that the treatment of SCC12 cells with GSP inhibited proliferation in a dose-dependent manner and reduced the motility and invasiveness of SCC12 cells through suppression of matrix metalloproteinase-2/9 expression. GSP treatment also resulted in induction of apoptosis and autophagy via generation of reactive oxygen species. The inhibition of autophagy by 3-methyladenine decreased GSP-induced cell death, which suggested that GSP-induced autophagy can promote cell death. The results of the present study suggested that autophagy functions as a death mechanism in SCC and provided a rationale for the use of GSP in combination with autophagy activators for treating cancers such as SCC.

Proanthocyanidins: novel treatment for psoriasis that reduces oxidative stress and modulates Th17 and Treg cells

“…Proanthocyanidins also inhibit LPS-induced inflammation via inhibiting the mRNA expression of TNF-α and IL-1β and suppressing MAPK and NF-κB signal pathways [60]. Moreover, related studies demonstrated strong anti-proliferative properties of proanthocyanidins in squamous carcinoma cells, with increased apoptosis and autophagy [16,61]. Furthermore, proanthocyanidins were shown to be excellent inhibitors of VEGF and had in vitro and in vivo anti-angiogenic properties that affected angiogenesis by inhibiting of VEGF expression, endothelial cell migration, and vascularization [64,69,70].…”

“…Proanthocyanidins belong to plant flavonoids, including catechin and epicatechin, and have antioxidant, anti-inflammatory, anti-angiogenesic, anti-proliferative, and immunomodulatory effects [16,[57][58][59][60][61][62][63][64][65]. Proanthocyanidins have been isolated from grapes, apples, metasequoia bark, cinnamon, aronia fruit, cocoa beans, bilberry, cranberry, black currant, and various other plants [16,66]. As powerful antioxidants and free-radical scavengers, proanthocyanidins have a wide range of application in the treatment for various OS-related complaints [67].…”

“…7Proanthocyanidins also decrease Th17/Treg ratios and expression levels of inflammatory cytokines and STAT3, and have been used to treat various immune-mediated diseases [15,59]. (8) Finally, proanthocyanidins slowed tumorigenesis by inhibiting cell proliferation, VEGF expression, and angiogenesis [16,62,64,69,70,73]. Hypothetical mechanisms of proanthocyanidins in the treatment of psoriasis are broadly summarized in terms of OS inhibition, mediation of proinflammatory signaling pathways, and regulation of T cells (Figure 2).…”

“…Increasing evidence indicates that proanthocyanidins offer effective and safe treatments for various diseases, including cardiovascular disease, diabetes, autoimmune arthritis, and squamous cell carcinoma, primarily by ameliorating OS, regulating cell differentiation, and inhibiting cell proliferation. However, few studies demonstrate the efficacy of proanthocyanidins in the treatment of psoriasis [11][12][13][14][15][16]. Because psoriasis is an immune-mediated, inflammatory disease that leads to OS and T-cell abnormalities, we reviewed the evidence of treatment potential of psoriasis.…”

A Comparative Study on Phytochemical Profiles and Biological Activities of Sclerocarya birrea (A.Rich.) Hochst Leaf and Bark Extracts

“…It was also reported that cytotoxicity increases with the degree of polymerization and the percentage of galloylation of procyanidins and the gallate group seems to interfere with crucial cell functions; the galloylation appears to be a crucial structural feature defining the activity and toxicity of phenolic mixtures [ 35 ]. The cytotoxic activity of procyanidins in different types of cancer is, finally, well documented [ 36 , 37 , 38 , 39 , 40 ]. Therefore, these considerations agree with the results shown in this paper, justifying both the greater in vitro antioxidant activity and the most effective antiproliferative action seen for MBE.…”