Dihydromyricetin-mediated inhibition of the Notch1 pathway induces apoptosis in QGY7701 and HepG2 hepatoma cells

Abstract

AIMTo investigate whether Dihydromyricetin (DHM) inhibits cell proliferation and promotes apoptosis by downregulating Notch1 expression.METHODSThe correlation between Notch1 and Hes1 (a Notch1 target molecule) expression in hepatoma samples was confirmed by qRT-PCR. In addition, MTT assays, flow cytometry and TUNEL analysis showed that DHM possessed strong anti-tumor properties, evidenced not only by reduced cell proliferation but also by enhanced apoptosis in QGY7701 and HepG2 hepatocellular carcinoma (HCC) cells. The expressions of Notch1, Hes1, Bcl-2 and Bax were determined by Western blot.RESULTSAmong the tested samples (n = 64), the expression levels of Notch1 (75% of patients) and Hes1 (79.7% of patients) mRNA in tumor tissues were higher than in the normal liver tissues. There was a negative correlation between the expression of Notch1 and the degree of differentiation and positively correlated with the Alpha Fetal Protein concentration. The viability of HCC cells treated with DHM was significantly inhibited in a dose and time-dependent manner. Apoptosis was induced in HepG2 and QGY7701 cell lines following 24 h of DHM treatment. After treatment with DHM, the protein expression of Notch1 was downregulated, the apoptosis-related protein Bax was upregulated and Bcl2 was downregulated. Notch1 siRNA further enhanced the anti-tumor properties of DHM.CONCLUSIONNotch1 is involved in the development of HCC and DHM inhibits cell proliferation and promotes apoptosis by down-regulating the expression of Notch1.

Effects of dihydromyricetin on ARPE‐19 cell migration through regulating matrix metalloproteinase‐2 expression

“…The results indicated that the concentration of DHM < 100 μM had no toxic effects on the ARPE‐19 cells (Figure B). Compared with the previous studies, DHM (100 μM) was shown to inhibit cell proliferation in the human hepatic cancer cells …”

“…Relevant studies have indicated that DHM can induce cell apoptosis in hepatocellular carcinoma cells through inhibiting cell proliferation in a p53‐dependent manner . Furthermore, Hou et al indicated that DHM suppressed the phosphorylation of NF‐κB, p38, and JNK, but not ERK 1/2 in LPS‐stimulated macrophages .…”

“…Relevant studies have indicated that DHM can induce cell apoptosis in hepatocellular carcinoma cells through inhibiting cell proliferation in a p53-dependent manner. 19,27,35 Furthermore, Hou et al indicated that DHM suppressed the phosphorylation of NF-κB, p38, and JNK, but not ERK 1/2 in LPS-stimulated macrophages. 16 The MAPK pathway, including JNK, ERK 1/2, and p38, plays an essential role in regulating multiprocesses such as cell migration, invasion, and proliferation.…”

“…Compared with the previous studies, DHM (100 μM) was shown to inhibit cell proliferation in the human hepatic cancer cells. 27…”

Trop2 Promotes Multidrug Resistance by Regulating Notch1 Signaling Pathway in Gastric Cancer Cells

“…Human Notch is a transmembrane receptor protein encoded by one of the Notch1-4 genes. The Notch pathway plays a central role in cell differentiation [30], proliferation [31,32], apoptosis [33], metastasis [34], and stem cell maintenance [35]. Knockdown of Notch1 is reported to decrease chemotherapy resistance in cancer [36,37], and Notch1 can increase the expression of MRP1 to promote cancer chemoresistance [38].…”