Cancer is a major health concern as the incidence is growing worldwide and still lacks successful therapies. Plant-derived functional foods are getting considerable attention, primarily due to their safety and therapeutic potential. Polyphenols are a group of mostly natural, water-soluble organic compounds.Here, we review the functions of selected polyphenols and their anticancer properties on numerous cancer cell lines and their mechanisms. The literature search was performed using the electronic database PubMed, Google scholar up to June 2020, with the following keywords-polyphenol, polyphenol anticancer, quercetin anticancer, resveratrol anticancer, curcumin anticancer, and kaempferol anticancer. Chemical structures of the selected polyphenols were obtained using the ChemDraw program. The initial search identified 40,554 polyphenols papers and among that, 2,559 were limited to polyphenol and cancer, 987 quercetin and cancer, 2,174 curcumin and cancer, 1,079 resveratrol and cancer, and 226 were limited to kaempferol and cancer.A total of 84 papers are included in this review paper. Most studies report the multiple anticarcinogenic properties of plant-derived polyphenols, including its inhibitory effects on the proliferation of cancer cells, tumor expansion, angiogenesis, inflammation, and metastasis. Besides, some studies shows potential synergistic effects when polyphenol treatment combined with chemotherapeutic agents. Anticancer effects of polyphenolic compounds like quercetin, curcumin, resveratrol, and kaempferol are investigated on numerous cancer cell lines and have shown prominent results. The present review provides a direction to determine the anticarcinogenic ability of the selected polyphenols in vitro and in vivo. Consequently, the use of polyphenols in cancer treatment should be investigated in-depth in the future.

No abstract

Sinensetin (SIN) has been reported to exhibit anti-inflammatory and anti-cancer activity. However, the cellular and molecular mechanism by which SIN promotes hepatocellular carcinoma (HCC) cell death remains unclear. In the present study, we investigated the induction of cell death by SIN and its underlying mechanism in HepG2 cells, an HCC cell line. We found that SIN significantly induced cell death in HepG2 cells, whereas the proliferation rate of Thle2, human liver epithelial cells, was unaffected by SIN. SIN-treated HepG2 cells were not affected by apoptotic cell death; instead, autophagic cell death was induced through the p53-mediated AMPK/mTOR signaling pathway. Inhibition of p53 degradation led to both autophagy and apoptosis in HepG2 cells. p53 translocation led to SIN-induced autophagy, whereas p53 translocation inhibited SIN-induced apoptosis. However, SIN showed apoptosis in the p53-mutant Hep3B cell line. Molecular docking simulation of the p53 core domain showed effective binding with SIN, which was found significant compared with the known p53 activator, RITA. Collectively, these data suggest that SIN may be a potential anti-cancer agent targeting autophagic cell death in human liver cancer.

Many different types of programmed cell death (PCD) have been identified, including apoptosis and necroptosis. Apoptosis is a type of cell death that is controlled by various genes. It is in charge of eliminating aberrant cells such as cancer cells, replenishing normal cells, and molding the body as it develops. Necroptosis is a type of programmed cell death that combines necrosis and apoptosis. In other words, it takes on a necrotic appearance, although cells die in a controlled manner. Various investigations of these two pathways have revealed that caspase-8, receptor-interacting serine/threonine-protein kinase 1 (RIPK1), and RIPK3 are crucial proteins in charge of the switching between these two pathways, resulting in the activation or inhibition of necroptosis. In this review, we have summarized the key proteins between apoptosis and necroptosis.

Gastric cancer is the common type of malignancy positioned at second in mortality rate causing burden worldwide with increasing treatment options. Prunetin (PRU) is an O-methylated flavonoid that belongs to the group of isoflavone executing beneficial activities. In the present study, we investigated the anti-proliferative and cell death effect of the compound PRU in AGS gastric cancer cell line. The in vitro cytotoxic potential of PRU was evaluated and significant proliferation was observed. We identified that the mechanism of cell death was due to necroptosis through double staining and was confirmed by co-treatment with inhibitor necrostatin (Nec-1). We further elucidated the mechanism of action of necroptosis via receptor interacting protein kinase 3 (RIPK3) protein expression and it has been attributed by ROS generation through JNK activation. Furthermore, through computational analysis by molecular docking and dynamics simulation, the efficiency of compound prunetin against RIPK3 binding was validated. In addition, we also briefed the pharmacokinetic properties of the compound by in silico ADMET analysis.