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Objective. Gastric cancer, one of the most common malignant tumors worldwide, arises from the gastric mucosal epithelium and severely affects patient health and quality of life. Luteolin (LUT) is a flavonoid found in vegetables and fruits with diverse functions. A large number of studies have confirmed that LUT has an antitumor effect. Therefore, this study is aimed at verifying whether LUT can exert antitumor effects in synergy with oxaliplatin (OXA). As such, we examined the effects of LUT, OXA, and their coadministration in a gastric adenocarcinoma cell line (SGC-7901). We used the MTT assay to quantify the proliferation of SGC-7901 cells, flow cytometry to detect the cell cycle and apoptosis, ELISA to detect the expression of cell-cycle-related proteins, and western blot to detect the expression of related apoptotic factors. The results of this study show that the combination of LUT and OXA inhibited SGC-7901 cell proliferation and induced apoptosis by altering cell-cycle proportions. In addition, the combination also activated Cyt c/caspase signaling in SGC-7901 cells. In summary, LUT synergy with OXA inhibited the proliferation of gastric cancer cells in vitro. The present study also elucidated the mechanism by which LUT potentiated the sensitivity of SGC-7901 cells to OXA through the Cyt c/caspase pathway. [ABSTRACT FROM AUTHOR]

Tyroserleutide (YSL) is an active, low-molecular-weight polypeptide with in vitro and in vivo anticancer effects on human hepatocellular carcinoma BEL-7402 cells. In this study, we studied the effects of YSL on PI3K/AKT in the BEL-7402 cells to explore its anti-tumor mechanism. Results showed that YSL could up-regulate the mRNA and protein expression of tumor suppressor PTEN and increase their activities, meanwhile inhibited the mRNA and protein expression of oncogene AKT and decreased the kinase activities of AKT and PDK1. The resuming balance effect of YSL between PTEN and AKT could prevent the transmission of tumor cell proliferation signals in the PI3K/AKT pathway. Inhibition of AKT would change the status of downstream effectors in the PI3K/AKT pathway: (1) inhibition of AKT up-regulated expression of cell cycle regulatory factors of downstream - P21 and P27 which repressed cell cycle and inhibited proliferation of tumor cells. (2) Inhibition of AKT decreased the phosphorylation level of MDM2, and then increased the protein level of P53 which would accelerate death proceeding of tumor cells. (3) Inactivation of AKT removed its inhibition effect on phosphorylation of Bad, which might decrease protein level of apoptosis inhibitor Bcl-2 and Bcl-XL, damaging mitochondria of tumor cells and inducing apoptosis. [ABSTRACT FROM AUTHOR]

Background: Chronic alcohol intake increases circulating endotoxin levels causing excessive inflammation that aggravates the liver injury. (E)‐2,3‐dimethoxy‐4′‐methoxychalcone (L6H21), a derivative of chalcone, has been found to inhibit inflammation in cardiac diseases and nonalcoholic fatty liver disease. However, the use of L6H21 in alcoholic liver disease to inhibit exotoxin‐associated inflammation has not been explored. In this study, we examined the effects of L6H21 on EtOH + LPS‐induced hepatic inflammation, steatosis, and liver injury and investigated the underlying mechanisms. Methods: C57BL6 mice were treated with 5% EtOH for 10 days, and LPS was given to the mice 6 hours before sacrificing. One group of mice was supplemented with L6H21 with EtOH and LPS. RAW264.7 cells were used to analyze the effects of L6H21 on macrophage activation. Results: EtOH + LPS treatment significantly increased hepatic steatosis and serum levels of alanine transaminase (ALT) and aspartate transaminase (AST), which were reduced by L6H21 treatment. EtOH + LPS treatment increased hepatic inflammation, as shown by the increased hepatic protein levels of Toll‐like receptor‐4, p65, and p‐IκB, and increased oxidative stress, as shown by protein carbonyl levels and reactive oxygen species formation, which were reduced by L6H21 treatment. In addition, L6H21 treatment markedly inhibited EtOH + LPS‐elevated hepatic protein levels of NLRP3, cleaved caspase‐1, cleaved IL‐1β, and caspase‐1‐associated apoptosis. Conclusions: Our results demonstrate that L6H21 treatment inhibits EtOH + LPS‐induced liver steatosis and injury through suppression of NLRP3 inflammasome activation. L6H21 may be used as an alternative strategy for ALD prevention/treatment. [ABSTRACT FROM AUTHOR]

We established both an acute and chronic cardiac toxicity rat model, which showed pretreatment with rutin attenuated pirarubicin-induced myocardial histopathological injury, electrocardiogram abnormalities, and cardiac dysfunction. Rutin also significantly reduced serum levels of MDA, BNP, CK-MB, CTnT, and LDH and increased serum SOD levels. Treatment with rutin and dexrazoxane resulted in an increase in Bcl-2/Bax ratio (p < 0.05) and reduction in JNK and Caspase-3 protein levels, compared to the pirarubicin group (all p < 0.05). Furthermore, rutin at a dose of 50 mg/kg significantly attenuated the above-mentioned alterations. Our study suggests the antioxidant and anti-apoptotic properties of rutin may be responsible for the cardioprotective effects observed. [ABSTRACT FROM AUTHOR]