Inhibition of hepatocellular carcinoma growth via modulation of the miR-221/SOX11 axis by curcumin and berberine.

Hepatocellular carcinoma (HCC) is a fatal malignancy that has limited treatment options. This study focused on the potential therapeutic effects of curcumin (CUR) and berberine (BBR) on the miR-221/SRY-box transcription factor 11 (SOX11) axis in HCC. We investigated the combined effects of CUR and BBR on HEPG2 and Huh7 cell survival and miR-221 expression using Cell Counting Kit-8 assays and RT-qPCR, respectively. Western blotting was used to detect changes in the apoptosis-related caspase-3/9 protein levels. We performed bioinformatics analysis and dual-luciferase assays and measured apoptotic protein levels to assess the role of the miR-221/SOX11 axis in mediating the effects of CUR-BBR. Both CUR and BBR suppressed HCC cell growth in a dose-dependent manner, with the most potent combined effect observed at a 2:1 ratio. CUR-BBR treatment significantly downregulated miR-221 expression, and miR-221 overexpression partially reversed the CUR-BBR-mediated decrease in cell survival. In addition, SOX11 was found to be a direct target of miR-221. CUR-BBR treatment upregulated SOX11 expression, and overexpression of SOX11 restored the inhibitory effects of CUR-BBR on cell growth, migration, and invasion and promoted apoptosis in the presence of miR-221. Furthermore, CUR-BBR activated pro-apoptotic proteins caspase-3/9 through the miR-221/SOX11 axis. The combined effect of CUR-BBR played an important role in inhibiting the growth of HCC cells. This combined effect was achieved by regulating the miR-221/SOX11 axis and activating the synthesis of pro-apoptotic proteins. Our findings highlight a promising combined therapeutic approach for HCC and underscore the importance of targeting the miR-221/SOX11 axis.

Hydroxyethyl Starch Curcumin Enhances Antiproliferative Effect of Curcumin Against HepG2 Cells via Apoptosis and Autophagy Induction.

It is well documented that curcumin (CUR), as a polyphenol molecule originated from turmeric, has many advantages such as antioxidative, anti-inflammatory, neuroprotective, and antitumor effects. However, because of its poor water solubility and low bioavailability, the biomedical applications of CUR are limited. So, in this study, we modified CUR with conjugation to a food-derived hydrophilic hydroxyethyl starch (HES) via an ester linkage to fabricate the amphiphilic conjugate HES-CUR prior to self-assembling into uniform nanoparticles (HES-CUR NPs). And, the results of the 1H NMR spectra and FT-IR spectrum showed successful synthesis of HES-CUR NPs; moreover, the solubility and the drug loading efficiency of CUR were significantly increased. Next, we further explored the differences on the antitumor effects between HES-CUR NPs and CUR in HepG2 cells, and the results of the CCK8-assay and cell counting experiment showed that HES-CUR NPs exhibited a more significant antiproliferative effect than that of CUR in HepG2 cells. And HepG2 cells were more sensitive to apoptosis induced by HES-CUR NPs as evidenced by flow cytometry, increased cytochrome c level, and decreased full length caspase-3 and Bcl-2 protein expressions. Additionally, we found that the efficacy of HES-CUR NPs against HepG2 cells might be related to the enhanced degree of mitochondrial damage (decrease of the mitochondrial membrane potential and ATP) and autophagy (increased levels of Beclin-1 and LC3-II proteins). So, the findings in this study suggest that HES-CUR NPs have a great application potential in antitumor efficacy and play an important role in multiple signal pathways.