Although a dietary phytochemical luteolin has been shown to regulate various anticancer mechanisms, a role of luteolin in autophagy regulation is mostly unidentified. Here, we investigated whether luteolin exhibits its anticancer effects by induction of apoptosis and autophagy in a p53-dependent manner in colon cancer cells. Cell viability was determined using trypan blue exclusion test. The expressions of proteins and mRNAs were measured by immunoblotting and reverse transcription polymerase chain reaction, respectively. Luteolin at 10 − 20 μM induced cytotoxicity in p53 wild-type HCT116 colon cancer cells but not in p53 mutant HT-29 cells and normal colon cells. Luteolin exhibited its anticancer effect by increasing p53 phosphorylation and p53 target gene expression, leading to apoptosis and cell cycle arrest in HCT116 cells. We identified that luteolin can induce autophagy in p53 wild-type cells but not in p53 mutant cells, suggesting that luteolin-induced autophagy is p53-dependent; however, chloroquine-mediated inhibition of autophagy did not alter cytotoxicity and apoptosis of cells treated with luteolin. In conclusion, the present data showed that luteolin inhibits the growth of HCT116 colon cancer cells through p53-dependent regulation of apoptosis and cell cycle arrest regardless of the induction of autophagy.

Altered cholesterol metabolism is believed to play a causal role in major pathophysiological changes in neurodegeneration. Several studies have demonstrated that the absence of apolipoprotein E (ApoE), a predominant apolipoprotein in the brain, leads to an increased susceptibility to neurodegeneration. Previously, we observed that genistein, a soy isoflavone, significantly alleviated apoptosis and tau hyperphosphorylation in SH-SY5Y cells. Therefore, we investigated the neuroprotective effects of dietary genistein supplementation (0.5 g/kg diet) in the cortex and hippocampus of wild-type C57BL/6 (WT) and ApoE knockout (ApoE^−/−) mice fed a high-fat diet (HFD) for 24 weeks. Genistein supplementation alleviated neuroinflammation and peripheral and brain insulin resistance. Reductions in oxidative and endoplasmic reticulum stress were also observed in ApoE^−/− mice fed a genistein-supplemented diet. Beta-secretase 1 and presenilin 1 mRNA levels and beta-amyloid peptide (Aβ) protein levels were reduced in response to genistein supplementation in ApoE^−/− mice but not in WT mice. Although the absence of ApoE did not increase tau hyperphosphorylation, genistein supplementation reduced tau hyperphosphorylation in both WT and ApoE^−/− mice. Consistent with this result, we also observed that genistein alleviated activity of c-Jun N-terminal kinase and glycogen synthase kinase 3β, which are involved in tau hyperphosphorylation. Taken together, these results demonstrate that genistein alleviated neuroinflammation, Aβ deposition, and hyperphosphorylation in ApoE^−/− mice fed an HFD.

Obesity is considered a risk factor for neurodegeneration. Because fermentation of soybean increases contents of various bioactive compounds with anti-obesity and anti-diabetic activities, we investigated the protective effect of doenjang, a Korean traditional fermented soybean paste, against neuroinflammation and neurodegeneration in the cortex and hippocampus of mice fed a high-fat (HF) diet. C57BL/6J mice were fed a low-fat diet, an HF diet, an HF-containing steamed soybean diet, or an HF-containing doenjang (DJ) diet for 11 weeks. Doenjang consumption alleviated hippocampal neuronal loss, which was increased by the HF diet. Accordingly, we observed higher cell proliferation and neurotrophic factor mRNA levels in the DJ group. Contents of oxidative metabolites and mRNA levels of oxidative stress- and neuroinflammation-related genes were lower in the DJ group compared to the HF group. Dietary doenjang reduced β-amyloid peptide (Aβ) levels by regulating gene expressions involved in Aβ production and degradation. Furthermore, doenjang consumption reduced tau hyperphosphorylation induced by HF feeding. Overall, doenjang was more effective than steamed soybean in suppressing neuroinflammation and neurodegeneration in mice fed an HF diet. These results suggest that bioactive compounds produced during the fermentation and aging of soybean may be involved in the enhanced neuroprotective effects of doenjang.