Pectolinarigenin (PEC), a natural flavonoid present in Cirsium chanroenicum and in some species of Citrus fruits, has various pharmacological benefits such as anti-inflammatory and anti-cancer activities. In the present study, we investigated the anti-cancer mechanism of PEC induced cell death caused by autophagy and apoptosis in AGS and MKN28 human gastric cancer cells. The PEC treatment significantly inhibited the AGS and MKN28 cell growth in a dose-dependent manner. Further, PEC significantly elevated sub-G1 phase in AGS cells and G2/M phase cell cycle arrest in both AGS and MKN28 cells. Apoptosis was confirmed by Annexin V and Hoechst 33342 fluorescent staining. Moreover, Immunoblotting results revealed that PEC treatment down-regulated the inhibitor of apoptosis protein (IAP) family protein XIAP that leads to the activation of caspase-3 thereby cleavage of PARP (poly-ADP-ribose polymerase) in both AGS and MKN28 cells in a dose-dependent manner. The autophagy-inducing effect was indicated by the increased formation of acidic vesicular organelles (AVOs) and increased protein levels of LC3-II conversion in both AGS and MKN28 cells. PEC shows the down regulation of PI3K/AKT/mTOR pathway which is a major regulator of autophagic and apoptotic cell death in cancer cells that leads to the down-regulation of p-4EBP1, p-p70S6K, and p-eIF4E in PEC treated cells when compared with the untreated cells. In conclusion, PEC treatment might have anti-cancer effect by down-regulation of PI3K/AKT/mTOR pathway leading to G2/M phase cell cycle arrest, autophagic and apoptotic cell death in human gastric cancer cells. Further studies of PEC treatment can support to develop as a potential alternative therapeutic agent for human gastric carcinoma.

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.

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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.