This study investigated whether kaempferol could inhibit ovarian cancer (OC) by activation of endoplasmic reticulum (ER) stress and autophagy, and tested its effect on the sensitivity of OC cells to cisplatin (cis-diamminedichloroplatinum, DPP). To study the effect of kaempferol on activation of ER stress and autophagy and find out whether its mechanism of action involves calcium (Ca2+), A2780 OC cells were cultured in DMEM/F12 for 24 h with or without kaempferol (40 μmol/l) in the presence or absence of autophagy or ER stress inhibitors or a calcium chelator. To study the effect of kaempferol on the sensitivity of OC cells to DPP and the potential involvement of modulation of protein kinase B (Akt) expression, A2780 OC were incubated with kaempferol and increasing concentrations of DPP (0-20 μmol/l) and then with kaempferol at its predetermined IC50 (6.8 μmol/l). Compared to control cells, kaempferol increased cell apoptosis (158 %) and decreased viability (53.17 %) and proliferation (49.17 %) of A2780 OC cells. Concomitantly, it increased the protein levels of GRP78, PERK, ATF6, IRE-1, LC3II, beclin 1, and caspase 4, thus suggesting activation of cytotoxic autophagy. This was mediated by increasing intracellular Ca+2 levels. In addition, kaempferol increased the sensitivity of A2780 cells to DPP (IC50 from 6.867 ± 0.99 to 3.73 ± 0.59 μmol/l) by decreasing the protein levels of p-Akt (0.31 ± 0.09 vs 0.12 ± 0.005). In conclusion, the findings of this study encourage the use of kaempferol alone or in combination with DPP to inhibit tumorigenesis of ovarian cells.

• MeSH
• apoptóza MeSH
• autofagie * MeSH
• cisplatina farmakologie   MeSH
• kempferoly farmakologie   MeSH
• lidé MeSH
• nádorové buněčné linie MeSH
• nádory vaječníků patologie   MeSH
• protoonkogenní proteiny c-akt antagonisté a inhibitory   metabolismus   MeSH
• signální transdukce MeSH
• stres endoplazmatického retikula účinky léků   MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

Annona and ginger have prominent uses in traditional medicine; their therapeutic properties have not been sufficiently explored. The ameliorative effect of Annona or ginger extracts on hyperglycaemia associated with oxidative stress, inflammation, and apoptosis in experimentally induced diabetes was addressed. Type 1 diabetes in male rats was induced by a single injection of streptozotocin (STZ; 40 mg/kg, i.p.), then Annona (100 mg/kg) or ginger (200 mg/kg) extracts were orally administered daily for 30 days. The Annona and ginger extracts ameliorated hyperglycaemia, insulin level, glycosylated haemoglobin (HbA1c) and insulin resistance (HOMA-IR) levels in the diabetic rats. The treatments significantly ameliorated liver function enzymes and total proteins; this was confirmed by histopathological examination of liver sections. Annona and ginger extracts significantly reduced elevated malondialdehyde (MDA) and restored activity of antioxidant enzymes in the liver such as glutathione peroxidase (GPx), glutathione reductase (GR), superoxide dismutase (SOD), and catalase (CAT) and the hepatic content of reduced glutathione (GSH). The oxidative stressdependent inflammation was regulated by both Annona and ginger extracts, which was indicated by down-regulation of TNF-α, NF-κB, pro-apoptotic proteins Bax, p53, and anti-apoptotic protein Bcl-2. Moreover, the expression of insulin receptor (INSR) and glucose transporter 2 (GLUT2) genes was markedly regulated by both these extracts. The results suggest that Annona and ginger extracts ameliorate the hepatic damage resulting from diabetes by advocating antioxidants and modulating apoptotic mediator proteins in the liver of diabetic rats. In conclusion, Annona and ginger extracts have a potential therapeutic effect in the treatment of diabetes and its complications.

• MeSH
• Annona chemie   MeSH
• antioxidancia metabolismus   MeSH
• apoptóza účinky léků   MeSH
• biologické markery krev   MeSH
• experimentální diabetes mellitus krev   farmakoterapie   enzymologie   MeSH
• glykovaný hemoglobin metabolismus   MeSH
• inzulin krev   MeSH
• inzulinová rezistence MeSH
• jaterní testy MeSH
• játra účinky léků   patofyziologie   MeSH
• krevní glukóza metabolismus   MeSH
• malondialdehyd metabolismus   MeSH
• nádorový supresorový protein p53 metabolismus   MeSH
• NF-kappa B metabolismus   MeSH
• oxidační stres účinky léků   MeSH
• potkani Wistar MeSH
• přenašeč glukosy typ 2 genetika   metabolismus   MeSH
• protein X asociovaný s bcl-2 metabolismus   MeSH
• receptor inzulinu genetika   metabolismus   MeSH
• regulace genové exprese MeSH
• rostlinné extrakty farmakologie   terapeutické užití   MeSH
• TNF-alfa metabolismus   MeSH
• zázvor lékařský chemie   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH