Quercetin up-regulates the expression of tumor-suppressive microRNAs in human cervical cancer.

Quercetin, a flavonol present in many vegetables and fruits, has been identified as a chemoprevention agent in several cancer models. However, the molecular mechanism of quercetin's anticancer activity is not entirely understood. MicroRNAs (miRNAs), small noncoding RNAs, have been reported to play key roles in various biological processes by regulating their target genes. We hypothesized that quercetin can exert an anticancer effect through the regulation of miRNAs. To test this hypothesis, we investigated the effects of quercetin on the expression of tumor-suppressive miRNAs in cervical cancer. Quercetin up-regulated the in vivo and in vitro expression of tumor-suppressive miRNAs miR-26b, miR-126, and miR-320a. Quercetin suppressed the level of ß-catenin, encoded by catenin beta 1 (CTNNB1), by up-regulating miR-320a in HeLa cells. Moreover, quercetin increased the expression of mir-26b, mir-126, and mir-320a precursors in HeLa cells. The results from this study show that quercetin has the potential to prevent cervical cancer by regulating the expression of tumor-suppressive miRNAs.

Soy isoflavone metabolite equol inhibits cancer cell proliferation in a PAP associated domain containing 5-dependent and an estrogen receptor-independent manner.

Isoflavone is a species of polyphenol found mainly in soy and soy products. Many studies have demonstrated its estrogen receptor (ER)-dependent action. Equol is an intestinal metabolite of a major soy isoflavone daidzein. We aimed to elucidate the mechanism for ER-independent actions of equol. Equol has been shown to inhibit proliferation of HeLa human cervical cancer cells and mouse melanoma B16 cells in an ER-independent manner. Using functional genetic screening, PAP associated domain containing 5 (PAPD5), which is a non-canonical poly(A) polymerase, was identified as an essential molecule in the ER-independent action. While peroral administration of equol inhibited tumor growth of control B16 cells subcutaneously inoculated in mice, it had little effect on the growth of PAPD5-ablated B16 cells. Intriguingly, equol progressed tumor growth of the PAPD5-ablated human breast cancer MCF-7 cells, which have high ERα expression. Equol has been found to induce polyadenylation of snoRNAs in a PAPD5-depdendent manner. Furthermore, peroral equol administration increased microRNA miR-320a expression in tumors. Together, these results suggest that equol may have a dual effect on ER-positive cancer cells, acting with, antiproliferative activity through PAPD5 and exhibiting proliferative activity via ERα and the former could be associated with miR-320a.

Delphinidin Prevents Muscle Atrophy and Upregulates miR-23a Expression.

Delphinidin, one of the major anthocyanidins, shows protective effects against a variety of pathologies, including cancer, inflammation, and muscle atrophy. The purpose of this study was to determine the preventive mechanism of delphinidin on disuse muscle atrophy. In vitro and in vivo models were used to validate the effects of delphinidin on the expression of MuRF1, miR-23a, and NFATc3. Delphinidin suppressed the upregulation of MuRF1 (1.77 ± 0.05 vs 1.03 ± 0.17, P < 0.05) expression and inhibited the downregulation of miR-23a (0.56 ± 0.05 vs 0.94 ± 0.06, P < 0.05) and NFATc3 (0.61 ± 0.02 vs 1.02 ± 0.08, P < 0.01) expression in dexamethasone-treated C2C12 cells. In gastrocnemius, muscle weight loss was prevented by oral administration of delphinidin. Moreover, delphinidin suppressed MuRF1 (3.35 ± 0.13 vs 2.26 ± 0.3, P < 0.01) expression and promoted miR-23a (0.58 ± 0.15 vs 2.25 ± 0.29, P < 0.001) and NFATc3 (0.85 ± 0.17 vs 1.54 ± 0.13, P < 0.001) expressions. Delphinidin intake may prevent disuse muscle atrophy by inducing miR-23a expression and suppressing MuRF1 expression.