Anticancer effects of dihydromyricetin on the proliferation, migration, apoptosis and in vivo tumorigenicity of human hepatocellular carcinoma Hep3B cells

Abstract

Background Hepatocellular carcinoma (HCC) represents a serious public health problem worldwide and has high morbidity and mortality. Dihydromyricetin (DHM) exhibits anticancer effect on a variety of malignancies, but its anticancer function of DHM in HCC has been unclear. The aim of this study was designed to investigate the anticancer effect of DHM on cell apoptosis, proliferation, migration and invasion of hepatoma carcinoma cells. Methods Cultured Hep3B cells were treated with different DHM concentrations, followed by cell apoptosis, proliferation, migration and invasion were examined by CCK-8, colony formation assay, wound healing, Transwell and flow cytometry, respectively. The mRNA and protein expression of BCL-2, Cleaved-caspase 3, Cleaved-caspase 9, BAK, BAX and BAD were validated by western blot. Results DHM markedly suppressed proliferation, migration, invasion and facilitated apoptosis in Hep3B cells. Mechanistically, DHM significantly downregulated the Bcl-2 expression, and upregulated the mRNA and protein levels of Cleaved-Caspase 3, Cleaved- Caspase 9, Bak, Bax and Bad. Furthermore, in the nude mice tumorigenic model, DHM treatment greatly decreased the weight of the HCC cancers compared to the weights in control and NDP group. Conclusions DHM could suppress cell proliferation, migration, invasion, and facilitated apoptosis in Hep3B cells. These findings could provide novel insights to develop potential therapeutic strategy for the clinical treatment of HCC.

A multifaceted review on dihydromyricetin resources, extraction, bioavailability, biotransformation, bioactivities, and food applications with future perspectives to maximize its value

“…In two human cholangiocarcinoma HCCC9810 and TFK‐1 cells, the mechanism of anti‐cancer actions of DMY was through the regulation of microRNA‐21(miR‐21)/ phosphatase and tensin homolog (PTEN)/Akt. While in Hep3B cells, it was via modulating the apoptotic signaling pathways of cell apoptosis and metastasis [87, 88]. Besides, apoptosis induction in human hepatocarcinoma HepG2 cells by DMY through activating the mitochondrial apoptosis and suppressing the Akt/Bad signaling pathway [89].…”

Analysis of the role of dihydromyricetin derived from vine tea (<i>Ampelopsis grossedentata</i>) on multiple myeloma by activating STAT1/RIG-I axis

“…Evidence indicates that DHM can directly restrain tumor growth in vivo [ 19 , 50 , 51 ]. For instance, DHM can inhibit tumor growth of nasopharyngeal cancer [ 50 ] and hepatocellular carcinoma [ 51 ] in xenograft mice.…”

Comprehensive review of Bcl‐2 family proteins in cancer apoptosis: Therapeutic strategies and promising updates of natural bioactive compounds and small molecules

“…In a recent study, the flavonoid dihydromyricetin, which is derived from vine tea, was shown to exhibit significant anticancer effects by effectively reducing the proliferation, migration, and invasion of Hep3B liver cancer cells (Jiang et al, 2021). Notably, it induced apoptosis in a dose-dependent manner.…”

“…Notably, it induced apoptosis in a dose‐dependent manner. Dihydromyricetin was able to upregulate proapoptotic regulatory proteins, including BAK, BAX, and BAD, while lowering the levels of the prosurvival protein Bcl‐2 (Jiang et al, 2021). Additionally, in vivo xenograft experiments demonstrated that dihydromyricetin significantly reduced tumor weight, highlighting its potential as an anticancer agent.…”